Showing papers by "Virginia Commonwealth University published in 1998"

Interferon Alfa-2b Alone or in Combination with Ribavirin as Initial Treatment for Chronic Hepatitis C

Abstract: Background Only 15 to 20 percent of patients with chronic hepatitis C have a sustained virologic response to interferon therapy. We compared the efficacy and safety of recombinant interferon alfa-2b alone with those of a combination of interferon alfa-2b and ribavirin for the initial treatment of patients with chronic hepatitis C. Methods We randomly assigned 912 patients with chronic hepatitis C to receive standard-dose interferon alfa-2b alone or in combination with ribavirin (1000 or 1200 mg orally per day, depending on body weight) for 24 or 48 weeks. Efficacy was assessed by measurements of serum hepatitis C virus (HCV) RNA and serum aminotransferases and by liver biopsy. Results The rate of sustained virologic response (defined as an undetectable serum HCV RNA level 24 weeks after treatment was completed) was higher among patients who received combination therapy for either 24 weeks (70 of 228 patients, 31 percent) or 48 weeks (87 of 228 patients, 38 percent) than among patients who received interfe...

A Comparison of Four Treatments for Generalized Convulsive Status Epilepticus

Abstract: Background and Methods Although generalized convulsive status epilepticus is a life-threatening emergency, the best initial drug treatment is uncertain. We conducted a five-year randomized, double-blind, multicenter trial of four intravenous regimens: diazepam (0.15 mg per kilogram of body weight) followed by phenytoin (18 mg per kilogram), lorazepam (0.1 mg per kilogram), phenobarbital (15 mg per kilogram), and phenytoin (18 mg per kilogram). Patients were classified as having either overt generalized status epilepticus (defined as easily visible generalized convulsions) or subtle status epilepticus (indicated by coma and ictal discharges on the electroencephalogram, with or without subtle convulsive movements such as rhythmic muscle twitches or tonic eye deviation). Treatment was considered successful when all motor and electroencephalographic seizure activity ceased within 20 minutes after the beginning of the drug infusion and there was no return of seizure activity during the next 40 minutes. Analyse...

Effects of Metformin on Spontaneous and Clomiphene-Induced Ovulation in the Polycystic Ovary Syndrome

Abstract: Background Obese women with the polycystic ovary syndrome are relatively unresponsive to the induction of ovulation by clomiphene. We hypothesized that reducing insulin secretion by administering metformin would increase the ovulatory response to clomiphene. Methods We performed oral glucose-tolerance tests before and after the administration of 500 mg of metformin or placebo three times daily for 35 days in 61 obese women with the polycystic ovary syndrome. Women who did not ovulate spontaneously were then given 50 mg of clomiphene daily for five days while continuing to take metformin or placebo. Serum progesterone was measured on days 14, 28, 35, 44, and 53, and ovulation was presumed to have occurred if the concentration exceeded 8 ng per milliliter (26 nmol per liter) on any of these days. Results Twenty-one women in the metformin group and 25 women in the placebo group were given clomiphene because they did not ovulate spontaneously during the first phase of the study. Among the 21 women given metfo...

Co-occurrence of Abuse of Different Drugs in Men The Role of Drug-Specific and Shared Vulnerabilities

Abstract: Background Previous research has demonstrated genetic and environmental influences on abuse of individual substances, but there is less known about how these factors may influence the co-occurrence of abuse of different illicit drugs. Methods We studied 3372 male twin pairs from the Vietnam Era Twin Registry. They were interviewed using the Diagnostic Interview Schedule, Version III, Revised to investigate the extent to which the abuse of different categories of drugs occurs together within an individual, as well as the possibility that genetic and environmental factors are responsible for observed co-occurrence. Co-occurrence was quantified using odds ratios and conditional probabilities. Multivariate biometrical modeling analyses were used to assess genetic and environmental influences on co-occurrence. Results Abusing any category of drug was associated with a marked increase in the probability of abusing every other category of drugs. We found evidence for a shared or common vulnerability factor that underlies the abuse of marijuana, sedatives, stimulants, heroin or opiates, and psychedelics. This shared vulnerability is influenced by genetic, family environmental, and nonfamily environmental factors, but not every drug is influenced to the same extent by the shared vulnerability factor. Marijuana, more than other drugs, was influenced by family environmental factors. Each category of drug, except psychedelics, had genetic influences unique to itself (ie, not shared with other drug categories). Heroin had larger genetic influences unique to itself than did any other drug. Conclusion There are genetically and environmentally determined characteristics that comprise a shared or common vulnerability to abuse a range of illicit drugs.

Quality of life and clinical outcomes in elderly patients treated with ventricular pacing as compared with dual-chamber pacing. Pacemaker Selection in the Elderly Investigators.

Abstract: Background Standard clinical practice permits the use of either single-chamber ventricular pacemakers or dual-chamber pacemakers for most patients who require cardiac pacing. Ventricular pacemakers are less expensive, but dual-chamber pacemakers are believed to be more physiologic. However, it is not known whether either type of pacemaker results in superior clinical outcomes. Methods The Pacemaker Selection in the Elderly study was a 30-month, single-blind, randomized, controlled comparison of ventricular pacing and dual-chamber pacing in 407 patients 65 years of age or older in 29 centers. Patients received a dual-chamber pacemaker that had been randomly programmed to either ventricular pacing or dual-chamber pacing. The primary end point was health-related quality of life as measured by the 36-item Medical Outcomes Study Short-Form General Health Survey. Results The average age of the patients was 76 years (range, 65 to 96), and 60 percent were men. Quality of life improved significantly after pacemake...

Factors affecting excitatory amino acid release following severe human head injury

Abstract: Object. Recent animal studies demonstrate that excitatory amino acids (EAAs) play a major role in neuronal damage after brain trauma and ischemia. However, the role of EAAs in patients who have suffered severe head injury is not understood. Excess quantities of glutamate in the extracellular space may lead to uncontrolled shifts of sodium, potassium, and calcium, disrupting ionic homeostasis, which may lead to severe cell swelling and cell death. The authors evaluated the role of EEAs in human traumatic brain injury. Methods. In 80 consecutive severely head injured patients, a microdialysis probe was placed into the gray matter along with a ventriculostomy catheter or an intracranial pressure (ICP) monitor for 4 days. Levels of EAAs and structural amino acids were analyzed using high-performance liquid chromatography. Multifactorial analysis of the amino acid pattern was performed and its correlations with clinical parameters and outcome were tested. The levels of EAAs were increased up to 50 times normal...

Perioperative Blood Transfusion and Postoperative Mortality

Abstract: Context.—The risks of blood transfusion have been studied extensively but the benefits and the hemoglobin concentration at which patients should receive a transfusion have not.Objective.—To determine the effect of perioperative transfusion on 30- and 90-day postoperative mortality.Design.—Retrospective cohort study.Setting.—A total of 20 US hospitals between 1983 and 1993.Participants.—A total of 8787 consecutive hip fracture patients, aged 60 years or older, who underwent surgical repair.Main Outcome Measures.—Primary outcome was 30-day postoperative mortality; secondary outcome was 90-day postoperative mortality. The "trigger" hemoglobin level was defined as the lowest hemoglobin level prior to the first transfusion during the time period or, for patients in the nontranfused group, as the lowest hemoglobin level during the time period.Results.—Overall 30-day mortality was 4.6% (n=402; 95% confidence interval [CI], 4.1%-5.0%); overall 90-day mortality was 9.0% (n=788; 95% CI, 8.4%-9.6%). A total of 42% of patients (n=3699) received a postoperative transfusion. Among patients with trigger hemoglobin levels between 80 and 100 g/L (8.0 and 10.0 g/dL), 55.6% received a transfusion, while 90.5% of patients with hemoglobin levels less than 80 g/L (8.0 g/dL) received postoperative transfusions. Postoperative transfusion did not influence 30- or 90-day mortality after adjusting for trigger hemoglobin level, cardiovascular disease, and other risk factors for death: for 30-day mortality, the adjusted odds ratio (OR) was 0.96 (95% CI, 0.74-1.26); for 90-day mortality, the adjusted hazard ratio was 1.08 (95% CI, 0.90-1.29). Similarly, 30-day mortality after surgery did not differ between those who received a preoperative transfusion and those who did not (adjusted OR, 1.23; 95% CI, 0.81-1.89).Conclusions.—Perioperative transfusion in patients with hemoglobin levels 80 g/L (8.0 g/dL) or higher did not appear to influence the risk of 30- or 90-day mortality in this elderly population. At hemoglobin concentrations of less than 80 g/L (8.0 g/dL), 90.5% of patients received a transfusion, precluding further analysis of the association of transfusion and mortality.

The role of social and cognitive processes in children's adjustment to community violence.

Abstract: This study examined associations of community violence exposure and psychological well-being among 99 8-12 year old children (M = 10.7 years) using home interviews with mothers and children. Both moderators and mediators of the links between violence exposure and well-being were tested. After demographics and concurrent life stressors were controlled for violence exposure was significantly associated with intrusive thinking, anxiety, and depression. Regression analyses indicated that intrusive thinking partially mediated associated between violence exposure and internalizing symptoms. Planned comparisons revealed that violence exposure had the strongest effect on well-being among children with low social support or high levels of social strains. Furthermore, children with high levels of intrusive thinking were most likely to show heightened internalizing symptoms when they had inadequate social support.

Use of the Acute Cardiac Ischemia Time-Insensitive Predictive Instrument (ACI-TIPI) To Assist with Triage of Patients with Chest Pain or Other Symptoms Suggestive of Acute Cardiac Ischemia: A Multicenter, Controlled Clinical Trial

Abstract: Background: Approximately 6 million U.S. patients present to emergency departments annually with symp­ toms suggesting acute cardiac ischemia. Triage decisions for these patients are important but remain difficult. Objective: To test whether computerized prediction of the probability of acute ischemia, used with electrocardi­ ography, improves the accuracy of triage decisions. Design: Controlled clinical trial. Setting: 10 hospital emergency departments in the midwestern, southeastern, and northeastern United States. Patients: 10 689 patients with chest pain or other symp­ toms suggestive of acute cardiac ischemia. Intervention: The probability of acute ischemia pre­ dicted by the acute cardiac ischemia time-insensitive pre­ dictive instrument (ACI-TIPI), either automatically printed or not printed on patients' electrocardiograms. Measurements: Emergency department triage to a cor­ onary care unit (CCU), telemetry unit, ward, or home. Other measurements were the bed capacity of the CCU relative to that of the telemetry unit; training or supervi­ sion status of the triaging physician; and patient diagnoses and outcomes based on clinical, electrocardiographic, and creatine kinase data. Results: For patients without cardiac ischemia, in hospi­ tals with high-capacity CCUs and relatively low-capacity cardiac telemetry units, use of ACI-TIPI was associated with a reduction in CCU admissions from 15% to 12%, a change of -16% (95% CI, -30% to 0%), and an increase in emer­ gency department discharges to home from 49% to 52%, a change of 6% (CI, 0% to 14%; overall P = 0.09). Across all hospitals, for patients evaluated by unsupervised resi­ dents, use of ACI-TIPI was associated with a reduction in CCU admissions from 14% to 10%, a change of -32% (CI, -55% to 3%); a reduction in telemetry unit admissions from 39% to 31 %, a change of -20% (CI, -34% to -2%); and an increase in discharges to home from 45% to 56%, a change of 25% (CI, 8% to 45%; overall P = 0.008). Among patients with stable angina, in hospitals with high-capacity CCUs, use of ACI-TIPI was associated with a reduction in CCU admissions from 26% to 13%, a change of -50% (CI, -70% to -17%), and an increase in dis­ charges to home from 20% to 22%, a change of 10% (CI, -29% to 71%; overall P = 0.02). At hospitals with highcapacity telemetry units, use of ACI-TIPI was associated with a reduction in telemetry unit admissions from 68% to 59%, a change of -14% (CI, -27% to 1 %), and an increase

The Treatment of Chronic Depression, Part 3: Psychosocial Functioning Before and After Treatment With Sertraline or Imipramine

Abstract: Background Previous research has suggested that depressed patients, and particularly chronically depressed patients, have significant impairments in many areas of their lives. While previous studies suggested that these "psychosocial" impairments improve following pharmacologic treatment, no large scale definitive study using multiple measures of psychosocial functioning has been reported. Method We assessed multiple domains of psychosocial functioning using interviewer-rated and self-report measures within the context of a 12-week acute treatment trial of sertraline and imipramine for patients with chronic depression (double depression and chronic major depression). We also compared the psychosocial functioning data of this sample before and after treatment with normative data available from published community samples. Results Chronically depressed patients manifested severe impairments in psychosocial functioning at baseline. After treatment with sertraline or imipramine, psychosocial functioning improved significantly. Significant improvements appeared relatively early in treatment (week 4). Despite these highly significant improvements in functioning during acute treatment, the study sample as a whole did not achieve levels of psychosocial functioning comparable to a comparator nondepressed community sample. However, patients who reached full symptomatic response (remission) during acute treatment did have levels of psychosocial functioning in most areas at endpoint that approached or equaled those of community samples. Conclusion These results indicate that successful antidepressant treatment with sertraline or imipramine can alleviate the severe psychosocial impairments found in chronic depression.

Latent class analysis of lifetime depressive symptoms in the national comorbidity survey.

Abstract: Objective:Although clinical trials have documented the importance of identifying individuals with major depression with atypical features, there are fewer epidemiological data. In a prior report, the authors used latent class analysis (LCA) to identify a distinctive atypical depressive subtype; they sought to replicate that finding in the current study.Method:Using the National Comorbidity Survey data, the authors applied LCA to 14 DSM-III-R major depressive symptoms in the participants’ lifetime worst episodes (N=2,836). Validators of class membership included depressive disorder characteristics, syndrome consequences, demography, comorbidity, personality/attitudes, and parental psychiatric history.Results:The best-fitting LCA solution had six classes. Four were combinations of atypicality and severity: severe atypical, mild atypical, severe typical, and mild typical. Syndrome severity (severe atypical and typical versus mild atypical and typical classes) was associated with a pronounced pattern of more ...

Multisensory Integration in the Superior Colliculus of the Alert Cat

Abstract: Wallace, Mark T., M. Alex Meredith, and Barry E. Stein. Multisensory integration in the superior colliculus of the alert cat. J. Neurophysiol. 80: 1006–1010, 1998. The modality convergence patterns...

Analysis of peak magnitude and duration of analgesia produced by local anesthetics injected into sympathetic ganglia of complex regional pain syndrome patients

Abstract: :Objective:Pain-relieving effects of lidocaine/bupivicaine local anesthetic (LA) and saline (S) block of sympathetic ganglia (stellate block, 4 patients; lumbar sympathetic block, 3 patients) were compared in 7 complex regional pain syndrome (CRPS) patients on a double-blind crossover basis

MR-visible medical device for neurological interventions using nonlinear magnetic stereotaxis and a method imaging

Abstract: The present invention comprises a device and method for targeted drug delivery, and especially intracranial inflsion or retroperfusion drug delivery using nonlinear magnetic stereotaxis in combination with magnetic resonance (MR) imaging and/or X-ray visualization. An MR-visible and/or X-ray visible drug delivery device is positioned by non-linear magnetic stereotaxis at a site such as an intracranial target site, its location is verified via MR imaging, and it is then used to deliver a biologically active material such as a diagnostic or therapeutic drug solution into that site (such as the brain) at constant or variable rates. The spatial distribution kinetics of the injected or infised drug agent may be monitored quantitatively and non-invasively using real-time MR-imaging such as water proton directional diffusion MR imaging, to establish the efficacy of targeted drug delivery.

A comparison of rectal diazepam gel and placebo for acute repetitive seizures.

Abstract: Background Acute repetitive seizures are readily recognizable episodes involving increased seizure frequency. Urgent treatment is often required. Rectal diazepam gel is a promising therapy. Methods We conducted a randomized, double-blind, parallel-group, placebo-controlled study of home-based treatment for acute repetitive seizures. Patients were randomly assigned to receive either rectal diazepam gel, at doses ranging from 0.2 to 0.5 mg per kilogram of body weight on the basis of age, or placebo. Children received one dose at the onset of acute repetitive seizures and a second dose four hours later. Adults received three doses — one dose at onset, and two more doses 4 and 12 hours after onset. Treatment was administered by a care giver, such as a parent, who had received special training. The number of seizures after the first dose was counted for 12 hours in children and for 24 hours in adults. Results Of 125 study patients (64 assigned to diazepam and 61 to placebo) with a history of acute repetitive s...

Function of TAF II -containing complex without TBP in transcription by RNA polymerase II

Abstract: Initiation of transcription of a gene from a core promoter region by RNA polymerase II requires the assembly of several initiation factors to form a preinitiation complex. Assembly of this complex1,2 is thought to be nucleated exclusively by the sequence-specific binding of the TFIID transcription factor complex, which is composed of the TATA-binding protein (TBP) and TBP-associated factors (TAFIIs) (refs 3, 4), to the different promoters. Here we isolate and characterize a new multiprotein complex that does not contain either TBP or a TBP-like factor but is composed of several TAFIIs and other proteins. This complex can replace TFIID on both TATA-containing and TATA-lacking promoters in in vitro transcription assays. Moreover, an anti-TBP antibody that inhibits TBP- and TFIID-dependent transcription does not inhibit activity of this new complex. These results indicate that TBP-free RNA polymerase II mediated transcription may be able to occur in mammalian cells and that multiple preinitiation complexes may play an important role in regulating gene expression.

Peer influences and drug use among urban adolescents: family structure and parent-adolescent relationship as protective factors.

Abstract: The moderating influences of family structure and parent-adolescent distress on the relationship between peer variables and drug use were examined in a predominantly African American sample of 630 10th graders at 9 urban high schools. Both peer pressure and peer drug use were significantly related to the reported frequency of drug use. The relationship between peer pressure and drug use was stronger among girls than boys, and also among adolescents in families without fathers or stepfathers. The association between peer pressure and drug use also increased as a function of the level of mother-adolescent distress among adolescents who were not living with fathers or stepfathers. Neither gender nor family structure moderated the relationship between peer drug models and drug use. However, the association between peer drug models and drug use increased as a function of the level of mother-adolescent distress.

Do too many cooks always spoil the stew? An experimental analysis of rent-seeking and the role of a strategic buyer

Abstract: Laboratory methods are used to evaluate the effects of institutional arrangements and rent-defending activity on rent-seeking auction outcomes. In part, Nash equilibrium predictions are a useful behavioral guide: As predicted, more rents are dissipated in perfectly-discriminating auctions, where the high-bidder wins, than in lotteries, where relative bids determine the chance of winning. Also as predicted, the introduction of a rent-defending buyer reduces social costs. Nevertheless, the social costs of rent-seeking consistently exceed predicted levels. Moreover, individual bidding, especially by buyers, deviates markedly from Nash predictions.

Septic shock : An analysis of outcomes for patients with onset on hospital wards versus intensive care units

Abstract: Objective: To determine if early interventions for septic shock were associated with reduced mortality. Design: Retrospective cohort study. Setting: University hospital intensive care unit (ICU) and general wards. Patients: Forty-one consecutive patients prospectively identified with positive blood cultures and septic shock. Although all patients were eventually treated in an ICU, ten (24%) patients were on a general ward at the onset of septic shock, and 31 (76%) were in an ICU setting. Interventions: None. Measurements and Main Results: Over a period of 9 mos, a cohort of 41 patients who had positive blood cultures and septic shock was prospectively identified. The 28-day crude mortality was 46% (19 deaths). We compared the management of septic shock and outcome for patients on a general ward vs. those patients in an ICU setting. Of the ten patients on the ward at time of shock onset (median age 55.5 yrs; median Acute Physiology and Chronic Health Evaluation [APACHE] II score of 18.5), seven (70%) died. In contrast, the 31 patients receiving intensive care when shock developed were older and more ill (median age 66 yrs; median APACHE II 24), yet had a mortality of 39% (12 deaths). The odds ratio (OR) for death for ward patients compared with ICU patients was 3.57 (p = .17). In a multivariate logistic regression analysis, two risk factors for mortality were important: APACHE II score (p =.015) and ward status (p = .08). Candida species in the bloodstream is known to have a high attributable mortality. When type of bloodstream pathogen (Candida species vs. bacteria) was added to the model, APACHE II (OR 2.64 for 10-unit increase) remained significant (p =.014), but ward status (OR 3.97) became statistically nonsignificant (p = .222). The patients who were on a general ward when their shock developed had a median delay of 67 mins before transfer to an ICU setting. Ward patients received an intravenous fluid bolus after a median delay of 27 mins, whereas those in the ICU who received a fluid bolus did so after a median of 15 mins (p =.48). Ward patients also had a median delay of 310 mins to receive inotropic support compared with a median 22.5 mins (p =.037) for the patients in an ICU setting when shock started. Conclusions: The data suggest that for patients with septic shock on wards, there were clinically important delays in transfer of patients to the ICU, receipt of intravenous fluid boluses, and receipt of inotropic agents. However, the most powerful predictors of mortality were APACHE II scores and bloodstream infection with Candida species.

An empathy‐humility‐commitment model of forgiveness applied within family dyads

Abstract: Forgiveness is described as requiring empathy for the offender, the humility to see oneself as being as fallible and needy as the offender, and courage to commit publicly to forgive. Research supports the model in individual therapy and psychoeducational groups in which the forgiver does not have to confront the offender. Family therapy, in which partners, parent–child dyads or siblings must confess their need for forgiveness and forgive face to face provides special challenges. Processes of forgiveness – empathy, humility and commitment – are understood to be the same as in any interpersonal forgiveness context; that is, they are thought to occur within dyads. Techniques compatible with several varieties of family therapies are summarized for applying the model in family therapy to encourage family members to forgive.

"Race" and the Construction of Human Identity

Abstract: Race as a mechanism of social stratification and as a form of human identity is a recent concept in human history. Historical records show that neither the idea nor ideologies associated with race existed before the seventeenth century. In the United States, race became the main form of human identity, and it has had a tragic effect on low-status "racial" minorities and on those people who perceive themselves as of "mixed race." We need to research and understand the consequences of race as the premier source of human identity. This paper briefly explores how race became a part of our culture and consciousness and argues that we must disconnect cultural features of identity from biological traits and study how "race" eroded and superseded older forms of human identity. It suggests that "race" ideology is already beginning to disintegrate as a result of twentieth-century changes.

Assortative mating for major psychiatric diagnoses in two population-based samples

Abstract: Background. Previous studies on assortment for psychiatric disorders have reported discrepant findings. We aimed to test whether there is a significant association for psychiatric diagnoses, including alcoholism, generalized anxiety disorder, major depressive disorder, panic disorder and phobias between husbands and wives in two population-based samples. We further evaluated whether marital resemblance occurs primarily within or across psychiatric disorders and if assortment for psychopathology is primary or secondary to assortment for correlated variables. Methods. A model for mate selection addressed whether the correlation between mates for psychiatric disorders arises from direct assortment (primary homogamy) or through correlation with other variables for which assortment occurs (secondary homogamy) or through cross-variable assortment. The model accounted for within-person co-morbidity as well as across-spouse data. Results. Findings suggested that a moderate degree of assortment exists both within and across psychiatric diagnoses. Only a small amount of the observed marital resemblance for mental illness could be explained by assortment for correlated variables such as age, religious attendance and education. Similar results were obtained for the two samples separately and confirmed in their joint analysis, revealing that the co-morbidity and assortment findings, except for the marital correlation for age, religious attendance and education, replicate across samples. Conclusions. Significant but moderate primary assortment exists for psychiatric disorders. The bias in twin studies that have ignored the small amount of assortment is negligible.

Competition, commercialization, and the evolution of nonprofit organizational structures

Abstract: This article explores competition both in settings where nonprofits compete among themselves and where they compete with for-profits. Growing competition among nonprofits raises questions as to the impacts of this rivalry. How does competition affect nonprofit behavior and does it cause nonprofits to become more commercial in orientation? Does it alter organizational structures and does it cause nonprofits to become less focused on their charitable missions? The answers to these questions can influence public policy toward the nonprofit sector. A definition of competition is presented and Porter's five competitive forces are introduced and used to explore competition in nonprofit marketplaces. Conditions under which commercialization is likely to occur are discussed and the nature of competition is then examined in settings where nonprofits compete in mixed (for-profit/nonprofit) markets. Organizational structures from the health care industry are then used to highlight the evolving legal structures that nonprofits employ in competition with for-profits. Five policy implications of the analysis are examined and the need for additional information is highlighted.

Maintenance Phase Efficacy of Sertraline for Chronic Depression: A Randomized Controlled Trial

Abstract: Context.—The chronic form of major depression is associated with a high rate of prevalence and disability, but no controlled research has examined the impact of long-term treatment on the course and burden of illness.Objective.—To determine if maintenance therapy with sertraline hydrochloride can effectively prevent recurrence of depression in the high-risk group of patients experiencing chronic major depression or major depression with antecedent dysthymic disorder ("double depression").Design.—A 76-week randomized, double-blind, parallel-group study, conducted from September 1993 to November 1996.Setting.—Outpatient psychiatric clinics at 10 academic medical centers and 2 clinical research centers.Intervention.—Maintenance treatment with either sertraline hydrochloride (n=77) in flexible doses up to 200 mg or placebo (n=84).Patients.—A total of 161 outpatients with chronic major or double depression who responded to sertraline in a 12-week, double-blind, acute-phase treatment trial and continued to have a satisfactory therapeutic response during a subsequent 4-month continuation phase.Main Outcome Measure.—Time to recurrence of major depression.Results.—Sertraline afforded significantly greater prophylaxis against recurrence than did placebo (5 [6%] of 77 in the sertraline group vs 19 [23%] of 84 in the placebo group; P=.002 for the log-rank test of time-to-recurrence distributions). Clinically significant depressive symptoms reemerged in 20 (26%) of 77 patients treated with sertraline vs 42 (50%) of 84 patients who received placebo (P=.001). With use of a Cox proportional hazards model, patients receiving placebo were 4.07 times more likely (95% CI, 1.51-10.95; P=.005) to experience a depression recurrence, after adjustment for study site, type of depression, and randomization strata.Conclusions.—Maintenance therapy with sertraline is well tolerated and has significant efficacy in preventing recurrence or reemergence of depression in chronically depressed patients.

Effects of the abused solvent toluene on recombinant N-methyl-D-aspartate and non-N-methyl-D-aspartate receptors expressed in Xenopus oocytes.

Abstract: Previous studies have shown that toluene, which is commonly abused, depresses neuronal activity and causes behavioral effects in both animals and man similar to those observed for ethanol. In this study, the oocyte expression system was used to test the hypothesis that toluene, like ethanol, inhibits the function of ionotropic glutamate receptors. Oocytes were injected with mRNA for specific N-methyl-D-aspartate (NMDA) or non-NMDA subunits and currents were recorded using conventional two-electrode voltage clamp. To enhance the low water solubility of toluene, drug solutions were prepared by mixing toluene with alkamuls (ethoxylated castor oil) at a 1:1 ratio (v:v) and diluting this mixture to the appropriate concentration with barium-containing normal frog Ringer solution. Alkamuls, up to 0.1%, had no significant effects on membrane leak currents or on NMDA-induced currents. Toluene, up to approximately 9 mM, had only minor effects on membrane leak currents but dose-dependently inhibited NMDA-mediated currents in oocytes. The inhibition of NMDA receptor currents by toluene was rapid, reversible and the potency for toluene's effects was subunit dependent. The NR1/2B subunit combination was the most sensitive with an IC50 value for toluene-induced inhibition of 0.17 mM. The NR1/2A and NR1/2C receptors were 6- and 12-fold less sensitive with IC50 values of 1.4 and 2.1 mM, respectively. In contrast, toluene up to approximately 9 mM did not inhibit kainate-induced currents in oocytes expressing GluR1, GluR1(+)R2 or GluR6 subunits. These results suggest that some of the effects of toluene on neuronal activity and behavior may be mediated by inhibition of NMDA receptors.

A Registry-Based Twin Study of Depression in Men

Abstract: Background The only large, registry-based twin study of depression using diagnostic criteria assessed by structured interview included only women. We present results from a comparable study of men. Methods Data were collected using a standardized telephone interview of men from the Vietnam Era Twin Registry. Both twins from 3372 pairs participated. Probandwise concordance rates and biometric modeling were used to analyze the data. Results The diagnosis of major depression (MD), as defined by DSM-III-R , and the subtype of severe/psychotic MD were significantly affected by genetic ( h 2 =0.36 and 0.39, respectively) and nonshared environmental ( e 2 =0.64 and 0.61, respectively) factors but not by family environmental factors. Dysthymia and mild and moderate MD were affected by family environmental ( c 2 =0.27, 0.08, and 0.14, respectively) and nonshared environmental ( e 2 =0.73, 0.92, and 0.86, respectively) factors but not by genetic factors. Early-onset (before age 30 years) and late-onset (after age 30 years) MD were significantly affected by genetic ( h 2 =0.47 and 0.10, respectively) and nonshared environmental ( e 2 =0.53 and 0.90, respectively) factors. Early-onset MD was significantly more heritable than late-onset MD. Conclusions The magnitude of genetic and environmental effects on depression in men is similar to that previously reported in women. Also similar to previous findings, more severe and earlier-onset depression may be more strongly affected by genetic factors, but differences in the reliability of reports of depression associated with severity may inflate estimates of the effect of the unique environment and deflate heritability estimates for less severe depression.