CCL8 and the Immune Control of Cytomegalovirus in Organ Transplant Recipients.

Monitoring of cytomegalovirus cell-mediated immunity is a promising tool for the refinement of preventative and therapeutic strategies posttransplantation. Typically, the interferon-γ response to T cell stimulation is measured. We evaluated a broad range of cytokine and chemokines to better characterize the ex vivo host-response to CMV peptide stimulation. In a cohort of CMV viremic organ transplant recipients, chemokine expression-specifically CCL8 (AUC 0.849 95% CI 0.721-0.978; p = 0.003) and CXCL10 (AUC 0.841, 95% CI 0.707-0.974; p = 0.004)-was associated with control of viral replication. In a second cohort of transplant recipients at high-risk for CMV, the presence of a polymorphism in the CCL8 promoter conferred an increased risk of viral replication after discontinuation of antiviral prophylaxis (logrank hazard ratio 3.6; 95% CI 2.077-51.88). Using cell-sorting experiments, we determined that the primary cell type producing CCL8 in response to CMV peptide stimulation was the monocyte fraction. Finally, in vitro experiments using standard immunosuppressive agents demonstrated a dose-dependent reduction in CCL8 production. Chemokines appear to be important elements of the cell-mediated response to CMV infection posttransplant, as here suggested for CCL8, and translation of this knowledge may allow for the tailoring and improvement of preventative strategies.

Systematic assessment of 50 children with selective mutism.

OBJECTIVE: To clarify the diagnostic significance of selective mutism (elective mutism in DSM-III-R). METHOD: Fifty children with selective mutism were evaluated systematically by means of semistructured clinical interviews and rating scales to obtain detailed diagnostic information. RESULTS: All 50 children met DSM-III-R criteria for social phobia or avoidant disorder and 24 (48%) had additional anxiety disorders. Clinical measures of anxiety and behavioral symptoms supported the presence of anxiety disorders as a characteristic of selectivity mute children. Only one case each of oppositional defiant disorder and attention-deficit hyperactivity disorder was found. CONCLUSIONS: Persistent selective mutism typically presents in the context of anxiety disorders.

Open fluoxetine treatment of mixed anxiety disorders in children and adolescents.

An open-label pilot study examined fluoxetine treatment in 16 outpatients (9-18 years old) with mixed anxiety disorders. Following nonresponse to psychotherapy, fluoxetine monotherapy was started at 5 mg daily and was increased weekly by 5 or 10 mg daily for 6-9 weeks until improvement occurred or to a maximum of 40 mg (children under 12) or 80 mg (adolescents). Among patients on fluoxetine, severity of illness ratings were "much improved" (mean final Clinical Global Impression scale score 2.8 +/- 0.7). Clinical improvement occurred in 10 of 10 patients with current separation anxiety disorder, 8 of 10 with social phobia, 4 of 6 with specific phobia, 3 of 5 with panic disorder, and 1 of 7 with generalized anxiety disorder. Mean time to improvement was 5 weeks. Mean doses were 24 mg (0.7 mg/kg) for children and 40 mg (0.71 mg/kg) for adolescents. Side effects were transient and included drowsiness (31% of patients), sleep problems (19%), decreased appetite (13%), nausea (13%), abdominal pain (13%), and excitement (13%). No patient developed disinhibition, akathisia, or suicidality. These preliminary findings suggest fluoxetine effectiveness in separation anxiety disorder and social phobia. Youths with only one anxiety disorder appeared to respond to lower doses of fluoxetine than patients with multiple anxiety disorders (0.49 +/- 0.14 versus 0.80 +/- 0.28 mg/kg, p < 0.05).

Interpersonal psychotherapy for depressed adolescents: a one-year naturalistic follow-up study.

OBJECTIVE: To report on a 1-year naturalistic follow-up study of 14 depressed adolescents who were treated for 3 months with interpersonal psychotherapy adapted for depressed adolescents (IPT-A). METHOD: The 14 depressed adolescents were contacted approximately 1 year after completion of 3 months of IPT-A to participate in an evaluation of depressive symptomatology, social functioning, and life events. Both self-report and clinician-rated measures were administered. RESULTS: Ten adolescents participated in the follow-up evaluation. Only one of them met criteria for an affective disorder. The majority of subjects reported few depressive symptoms and had maintained their improvements in social functioning since completion of treatment for depression. The life events survey suggested that the subjects had experienced a significant number of negative life events during their lifetime. There were no reported hospitalizations, pregnancies, or suicide attempts since completion of treatment, and all were attending school regularly. CONCLUSIONS: Despite the limitations of a naturalistic follow-up and the small sample size, the results suggest that the adolescents maintained their state of recovery from depression until 1 year after completing treatment with IPT-A.

Distance education for nurse practitioners: a partial solution.

Health professionals who live and practice in rural areas have limited opportunities to further their education. In order to pursue advanced nursing degrees, nurses have to leave their communities. A collaborative distance education project involving the University of New Mexico College of Nursing, the Area Health Education Center, and Western New Mexico University has provided a partial solution to this problem. Six registered nurses living and practicing in a rural site are now receiving their Family Nurse Practitioner degrees via two-way audio/video teleconferencing equipment. Distance education can improve the numbers of primary care providers in rural areas; however, projects will require extensive planning and resources.

Free bladder mucosal graft biology: unique engraftment characteristics in rabbits.

To study the biology of bladder mucosal grafts we developed an animal model using New Zealand white male rabbits. A 25 x 9 mm. segment of bladder mucosa was harvested and tubularized over an 8F catheter using 7-zero polyglactin sutures. An equivalent portion of rabbit urethra was then excised and the graft was anastomosed to this defect in an end-to-end fashion. A urethral catheter was left in place to provide bladder drainage and to stent the anastomosis. Animals were sacrificed on postoperative days 1 to 90. India ink was injected into the aorta at sacrifice to visualize the microvasculature. All 59 specimens were stained with hematoxylin and eosin, and studied using light microscopy. Our results demonstrated vascular ingrowth at 72 hours. Between postoperative days 8 and 10 healthy viable epithelium first bridged the entire urethral defect. By postoperative day 12 the epithelial lining was complete. A poor outcome was observed in all animals whose stents were removed early. We conclude that the biology of bladder mucosal grafts is unique in that the graft initially undergoes partial degeneration followed by regeneration. Of concern are the results of those animals whose stents were removed early. In all such cases a poor outcome was observed.

The pharmacotherapy of moral or religious scrupulosity.

Moral or religious scrupulosity is a disabling condition which is sometimes seen in patients with obsessive compulsive disorder (OCD). The authors described 10 patients with moral or religious scrupulosity who were treated with fluoxetine or clomipramine. Seven of the 10 patients completed open treatment of at least 8 weeks without requiring adjunctive medication; 5 of those 7 patients were rated as much improved. Among the 3 patients who required adjunctive medication, 1 was rated as much improved. Of the 4 nonresponders at 3 months, 2 responded after longer treatment trials. These results suggest that extreme moral or religious concerns and behaviors might be a form of OCD and that the scrupulosity can be effectively treated with serotonin reuptake blockers.

A risk of malignancy index incorporating CA 125, ultrasound and menopausal status for the accurate preoperative diagnosis of ovarian cancer.

Age, ultrasound score, menopausal status, a clinical impression score and serum CA 125 level were assessed to see how they could best distinguish between patients with benign (n = 101) and malignant (n = 42) pelvic masses. Each criteria used alone provided statistically significant discrimination. The most useful individual criteria were a serum CA 125 level of 30 U/ml (sensitivity 81%, specificity 75%) and an ultrasound score of 2 (sensitivity 71%, specificity 83%). Three criteria could be combined in a risk of malignancy index (RMI) which is simply calculated using the product of the serum CA 125 level (U/ml), the ultrasound scan result (expressed as a score of 0, 1 or 3) and the menopausal status (1 if premenopausal and 3 if postmenopausal). This index was statistically virtually as effective a discriminant between cancer and benign lesions as more formal methods. Using an RMI cut-off level of 200, the sensitivity was 85% and the specificity was 97%. Patients with an RMI score of greater than 200 had, on average, 42 times the background risk of cancer and those with a lower value 0.15 times the background risk.

Treatment of depersonalization with serotonin reuptake blockers.

Eight patients with depersonalization disorder or with depersonalization symptoms in association with obsessive-compulsive and panic disorders were treated with serotonin reuptake blockers. There was clinical overlap of depersonalization disorder with obsessive-compulsive disorder, and the co-occurrence of obsessive-compulsive and panic features with depersonalization in these patients was associated with a favorable treatment outcome. The chronicity of illness and lack of prior response to a variety of treatments in these patients highlights the positive outcome with this treatment. In addition, issues are raised regarding the current hierarchical exclusion of depersonalization disorder in the presence of obsessive-compulsive and panic disorders.

Fluoxetine in panic disorder.

Twenty-five patients with a primary DSM-III-R diagnosis of panic disorder with or without agoraphobia were treated openly with the serotonin uptake inhibitor fluoxetine for up to 12 months. For most patients, treatment was initiated at 5 mg/day to minimize adverse effects previously reported with initiation at higher doses. Nineteen (76%) experienced moderate to marked improvement in panic attacks. Four (16%) were unable to tolerate fluoxetine due to adverse effects. Initiating treatment of panic disorder with low doses of fluoxetine may increase its acceptability and permit more patients to benefit from fluoxetine.

Fluoxetine treatment of obsessive-compulsive disorder: an open clinical trial.

The selective serotonin reuptake blocker fluoxetine was administered to 49 patients with obsessive-compulsive disorder in a 12-week open clinical trial. A minimum adequate trial of at least 8 weeks of treatment was completed by 39 patients. Response rates were 62% (24/39) of adequately treated patients and 49% (24/49) of the whole sample. These uncontrolled findings suggest that fluoxetine is of significant benefit for a substantial proportion of obsessive-compulsive disorder patients. However, controlled trials comparing fluoxetine with placebo and other active agents are needed to confirm this, as are studies aimed to delineate fluoxetine's full dose range, optimal length of treatment and relapse rate following discontinuation.