Recombinant human interleukin-10 fails to alter proinflammatory cytokine production or physiologic changes associated with the Jarisch-Herxheimer reaction.

Interleukin (IL)-10 may have a role in the treatment of cytokine-associated inflammatory syndromes. The Jarisch-Herxheimer reaction (J-HR), which follows antibiotic treatment of Borrelia recurrentis infection, is a useful model of acute systemic inflammation associated with a cytokine surge and characteristic pathophysiologic changes. In a double-blind, placebo-controlled study, 49 Ethiopian men with B. recurrentis infection were randomized to receive a single intravenous bolus of either 25 microg/kg of recombinant human (rh) IL-10 or vehicle control shortly before receiving intramuscular penicillin. Patients were monitored for physiologic changes, and plasma samples were taken repeatedly for 24 h after treatment. rhIL-10 had no impact on changes in any of the physiologic parameters of J-HR, plasma cytokine levels, or the rate of spirochete clearance. A single intravenous bolus of 25 microgram/kg of rhIL-10 does not seem to have a useful role in the treatment of the J-HR associated with B. recurrentis infection.

Interleukin-10: potential benefits and possible risks in clinical infectious diseases.

Human interleukin-10 (IL-10) is a potent anti-inflammatory cytokine that inhibits the synthesis of the major proinflammatory cytokines and chemokines. IL-10 is the principal TH2-type cytokine that upregulates humoral immune responses and attenuates cell-mediated immune reactions. This cytokine has a number of immunomodulatory properties that might be clinically useful in a variety of inflammatory and infectious disease states. Clinical trials with human recombinant IL-10 are already in progress. Carefully selected patients with inflammatory conditions may benefit from IL-10 therapy if concomitant infectious diseases are recognized and treated appropriately.

IL-10 as a therapeutic strategy in the treatment of rheumatoid arthritis.

IL-10 has anti-inflammatory and immunoregulatory properties that suggest a potential therapeutic role in RA. IL-10 inhibits proinflammatory cytokine and chemokine production in addition to blocking T-cell responses to specific antigens. It acts primarily through inhibition of costimulatory properties of macrophages. IL-10 stimulates proliferation and differentiation of antibody-forming B-cells. Preclinical studies in a variety of animal models, including collagen-induced arthritis, have shown that IL-10 is effective in preventing or inhibiting inflammation and autoreactivity. Although in RA, circulating and synovial levels of IL-10 are increased, accumulated evidence suggests that there may be a relative deficit of available IL-10. Moreover, exogenous addition of IL-10 in vitro has been shown to affect the immunopathological processes involved in RA. Preliminary studies of human recombinant IL-10 in patients with RA have demonstrated a trend towards efficacy with a good safety profile. Taken together, the data support a therapeutic role for IL-10 in the treatment of RA.

School age children's coping with sexual abuse: abuse stresses and symptoms associated with four coping strategies.

Strategies used by 84 sexually abused children, ages 7 to 12, to cope with their abuse were evaluated, along with child abuse-related symptoms, parent-reported behavioral symptoms, and teacher-reported behavioral symptoms. Principal components analysis of coping yielded four strategies that were labeled avoidant coping, internalized coping, angry coping, and active/social coping. Each coping strategy was found to be associated with a unique set of abuse characteristics, abuse-related social environment, and symptoms. In contrast to findings with adult survivors and adolescents, use of avoidant coping strategies among school-age children was found to be related to fewer behavioral problems, although it was also associated with greater sexual anxieties. Internalized coping was found to be associated with increased guilt and PTSD hyperarousal symptoms. Active/social coping was the only strategy found to be unrelated to symptoms, but neither was it associated with measured benefits. In contrast to some clinical opinion that externalizing blame and venting anger is a helpful strategy, angry coping was found to be associated with a wide range of behavioral and emotional problems as rated by the child's home-room school teacher. Results are discussed in terms of a proposed mediational model.

Internalizing and externalizing characteristics of sexually and/or physically abused children.

This study evaluates the behavioral consequences of childhood abuse (sexual, physical, or both), with particular focus on prevalence of posttraumatic stress disorder (PTSD). Three abuse type groups and nonabused controls were contrasted on behavioral rating scales and on structured psychiatric interview data. The participants (109 abused children and 16 normal control children) were recruited from Arkansas Children's Hospital and local agencies for abused children. As expected, proportionately more females than males were sexually abused. Overall, males were rated as more disturbed than females. Type of abuse did not consistently influence behavioral ratings. Externalizing scores were significantly higher than internalizing scores in all abused groups. PTSD was diagnosed in 50% of the abused children, with a higher rate for boys who had been sexually abused as opposed to physically abused only (58% versus 13%). The most frequent comorbid condition with PTSD was Separation Anxiety. Sexually abused boys were hospitalized for psychiatric treatment at a higher rate than were other abused children.

The relations between sociotropy and autonomy, positive and negative affect and two proposed depression subtypes.

We examined relations between the cognitive/personality model of sociotropy (SOC) and autonomy (AUT; Beck, 1983) and the affect/personality model of positive affect (PA) and negative affect (NA; Tellegen, 1985; Watson & Clark, 1984, 1992), and their relations to two proposed depression subtypes (Beck, 1983) in 60 adult depressed out-patients. SOC and NA scores shared significant common variance while facets of AUT and low PA were moderately related. Autonomous depressive symptoms appeared more depression-specific than sociotropic depressive symptoms. Findings did not confirm the usefulness of sociotropy and autonomy in the prediction of the symptom clusters, possibly due to the measurement of the depressive symptom clusters.

The process and outcomes of care for major depression in rural family practice settings.

Although primary care physicians provide the majority of care for rural residents with major depression, little is known about the quality of the care they provide. The aim of this study was to characterize the process and outcomes of care for rural patients with major depression, and to examine the relationship between the process and outcomes of care in this population. Six hundred and thirty-one patients in 21 primary care practices in small towns were screened; 47 patients (7.4% of patients screened) meeting DSM-III-R criteria for current major depression were recruited into the study, and 38 (81.0% of patients recruited) were followed an average of five months later using the Depression Outcomes Module (Rost, Smith, Burnam, & Burns, 1992). While 24 (63.1%) of the 38 depressed subjects received a prescription for one or more antidepressants between the index visit and follow-up, only 11 (28.9%) received pharmacologic treatment in concordance with the new Agency for Health Care Policy and Research (AHCPR) guidelines; 26 (68.4%) of 38 depressed patients continued to meet criteria for major depression at five months. Those who received pharmacologic treatment concordant with AHCPR guidelines showed more improvement at follow-up. The findings suggest that outcomes for major depression may be worse in rural family practice settings than in urban settings. The study also demonstrates that AHCPR guidelines define effective treatment for major depression in the study sample. The Depression Outcomes Module appears to be a reliable and valid instrument for monitoring the outcomes of care for major depression in family practice settings.

The mediating role of anxiety in self-reported somatic complaints of depressed adolescents.

This study examined the mediating role of anxiety in the self-reports of somatic complaints in 96 depressed adolescent inpatients. Sixty-four subjects with major depressive episodes and comorbid anxiety disorders (MDE-A) determined from the Diagnostic Interview for Children and Adolescents--Revised (DICA-R) reported significantly more somatic complaints than 32 adolescents having major depressive episodes without comorbid anxiety (MDE). An analysis of covariance demonstrated that, with anxiety symptoms controlled, MDE and MDE-A groups did not differ significantly in somatic complaints. A hierarchical multiple-regression analysis revealed that, with demographic and anxiety symptoms controlled, depressive symptoms did not contribute to the explanation or prediction of somatic complaints. The results suggest that anxious, but not depressive symptoms, are independently associated with somatic complaints. The results are discussed in light of new affective models of psychopathology.

Gender and the comparison of self and observer ratings of anxiety and depression in adolescents.

OBJECTIVE: This study assessed the influence of gender on the comparability of self and observer ratings of anxiety and depression in adolescents. METHOD: Subjects were 75 inpatient adolescents who were administered structured interviews of the revised Hamilton Rating Scales for Depression (HRSD-R) and Anxiety (HARS-R) and read the Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI). RESULTS: All measures demonstrated adequate internal consistency and validity. The correlation between the BDI and HRSD-R was significantly higher for females than males; of 11 symptoms that overlap on the BDI and HRSD-R, observers significantly agreed with males and females in their perceptions of 5 and 11 depressive symptoms, respectively. The correlation between the BAI and HARS-R did not differ significantly for males and females. CONCLUSIONS: Results suggest that self-reports of anxiety symptoms are a valid, cost-effective alternative to anxiety observer ratings for boys and girls' self-reports of depression are comparable to depression ratings by observers. There is the need to collect self-report information from adolescent boys because they may not communicate subjective symptoms of depression, e.g., guilt, to observers.

Integration of positive and negative affectivity and cognitive content-specificity: improved discrimination of anxious and depressive symptoms.

In a sample of 159 psychiatric outpatient adults, negative affectivity (NA) was significantly correlated with a broad range of anxiety and depressive symptoms and was not useful for the differentiation of anxiety from depression. Low positive affectivity (PA) was significantly related only to depressive symptoms. Whereas depressive cognitions demonstrated discriminant capability, anxiety cognitions (in isolation) demonstrated nonspecificity. A combination of NA and anxious cognitions significantly predicted anxiety symptoms, better than did cognitions or affect alone. NA, depressive cognitions, and low PA significantly predicted depressive symptoms. Results support the integration of affective and cognitive models for the discrimination of anxious from depressive symptoms and have implications for measure development. Modifications in the cognitive content-specificity theory of anxiety states are discussed.

Clinical safety, tolerability, and pharmacokinetics of murine monoclonal antibody to human tumor necrosis factor-alpha.

The safety, tolerability, and pharmacokinetic profile of murine monoclonal antibody to human tumor necrosis factor-alpha (TNF alpha MAb) were evaluated in 20 uninfected patients at risk of sepsis and 16 septic patients. TNF alpha MAb was well tolerated in all patients, with no immediate or delayed signs of allergic reaction. During the 28-day evaluation, side effects included thrombocytosis (11), hepatic enzyme elevations (8), cardiac arrhythmias (3), and deaths (5). Each was attributed to the patient's severe underlying disease and not to TNF alpha MAb; however, a relationship between TNF alpha MAb and these events cannot be ruled out. The half-life was 52 h for a single infusion of TNF alpha MAb. Human antibody against TNF alpha MAb was observed in 13 (76.5%) of 17 phase IA patients and 10 of 10 phase IB patients and anti-idiotype antibodies in 11 (91.7%) of 12 phase IA patients and 2 (33.3%) of 6 phase IB patients. TNF alpha MAb should be evaluated as adjunctive therapy for patients with sepsis.

Tumor necrosis factor and the therapeutic potential of anti-tumor necrosis factor antibodies.

OBJECTIVE: To review the relationship of tumor necrosis factor (TNF) to clinical sepsis and the clinical potential of anti-TNF therapy in decreasing morbidity and mortality rates due to sepsis. DATA SOURCES: The international English language literature was reviewed, including animal studies and human clinical trials regarding TNF, anticytokine therapy, and sepsis. STUDY SELECTION: Studies which characterized the immunopharmacologic interactions between TNF and sepsis were emphasized. DATA EXTRACTION: This study specifically focused on experiments and clinical trials that directly involve the activity of TNF or anti-TNF antibodies, particularly but not limited to data derived from septic patients. DATA SYNTHESIS: The relationship between TNF and sepsis is described. Clinical aspects of anti-TNF therapy (timing, empiric use) are discussed. Phase I, II, and III trail of anti-TNF antibodies in clinical trials are reviewed. CONCLUSIONS: Current clinical strategies for sepsis therapy are only partially effective. Recent immunopharmacologic advancements have resulted in the identification of TNF as a pivotal proinflammatory cytokine mediator of sepsis. Animal studies demonstrate that anti-TNF therapy protects animals from the morbidity and mortality of sepsis. Phase I clinical studies of anti-TNF antibodies demonstrate the safety of monoclonal antibody therapy. The therapeutic application of anti-TNF antibodies in sepsis trials is ongoing.

Differential diagnosis and treatment of conversion disorder and Guillain-Barre syndrome.

Three cases are presented which illustrate the possible difficulties in differentiating between the diagnoses of Guillain-Barre Syndrome and conversion disorder. Accepted criteria are specified for each condition, as well as some associated features often characteristic of similar cases. Supportive interdisciplinary treatment for Guillain-Barre Syndrome is reviewed, and an interdisciplinary multi-modal approach to treatment of conversion disorder is described.

Regulation of gamma interferon production by natural killer cells in scid mice: roles of tumor necrosis factor and bacterial stimuli.

CB-17 scid mice exhibit a T-cell-independent but gamma interferon (IFN-gamma)-dependent immunity to Listeria monocytogenes. In this study, we analyzed the specific cellular interactions involved in this process. scid mouse-derived natural killer (NK) cells cultured with heat-killed (HK) L. monocytogenes and macrophages secreted IFN-gamma. No IFN-gamma was produced in cultures containing HK L. monocytogenes but lacking macrophages. However, medium derived from macrophages incubated with HK L. monocytogenes or other microorganisms stimulated IFN-gamma production by isolated NK cells. Treatment of macrophage-conditioned supernatants with neutralizing monoclonal anti-tumor necrosis factor (TNF) significantly reduced their capacity to stimulate NK cells to produce IFN-gamma. Yet, purified recombinant TNF-alpha by itself was unable to stimulate NK cells. Thus, TNF was necessary but not sufficient to induce maximal IFN-gamma production by NK cells. Sonicated L. monocytogenes stimulated production of IFN-gamma by NK cells that was resistant to anti-TNF. Stimulation was markedly enhanced by the addition of recombinant TNF-alpha. These studies demonstrated that activation of scid NK cells for secretion of IFN-gamma requires two signals: TNF-alpha and a second product which may be of bacterial origin and may require processing by mononuclear phagocytes. We suggest that the T-cell-independent production of IFN-gamma by NK cells provides the host with a rapid mechanism to temporarily heighten nonspecific resistance to infection until such time as T-cell-dependent sterilizing immune responses can be generated.

CPQ personality factors of upper elementary gifted students.

The results of administering the Children's Personality Questionnaire (CPQ) to gifted students in the fourth, fifth, and sixth grades indicated that they had personality profiles similar to the norm group. Gifted males were more controlled, socially precise, self-disciplined, and compulsive than females, described as more casual and careless of social rules. Also, gifted females were more assertive and independent than males who had scores suggesting a more obedient, mild, or conforming personality. In comparing personality factors across grades, fourth graders had profiles significantly different from sixth graders.

A comparison of verbal, sign, and simultaneous systems for the acquisition of receptive language by an autistic boy.

The effectiveness of verbal, sign, and simultaneous systems for the acquisition of receptive language by an autistic boy was investigated. The subject received training in all three methods by three teachers on each of 18 days. The order of methods and teachers was counterbalanced daily. The study incorporated a 27-word vocabulary composed of nouns, adjectives (colors), and verbs. The dependent variable was the number of correct responses during three daily sets of 20 assessment trials. Results suggest nonsignificant differences among the three methods. A secondary purpose was to investigate systematically the concomitant increases in subject-initiated interactions and eye contact accompanying the language training. The subject was observed during 10-min rest periods following each of the three daily language sessions; the occurrence of behaviors during timed intervals served as the dependent variables. Significant increases for subject-initiated interactions involving physical contact were observed.