Trends Influencing Future Delivery of Mental Health Services in Large Healthcare Systems

The delivery of mental health services, particularly psychotherapy and other psychosocial care, is being increasingly limited by financial constraints. We briefly review three trends that will play an increasingly important role in the delivery of mental health services in large organizations such as health maintenance organizations. These are (a) an increasing role for self-help and bibliotherapy interventions, both in traditional and electronic formats; (b) mental health services being offered in settings other than mental health specialty clinics; and (c) an increased emphasis on mechanisms for improving the quality and type of services offered, including quality improvement methods and pay-for-performance.     

Uncovering novel inter- and intrachromosomal chromosome 1 aberrations in follicular lymphomas by using an innovative multicolor banding technique

Follicular lymphoma (FL) is characterized by t(14;18)(q32;q21), which is the initial genetic perturbation in this disease. Additional genetic mutations are required to generate a fully malignant phenotype. Secondary chromosomal alterations seen in FL include prominent involvement of chromosome 1 in the form of balanced or unbalanced translocations, insertions, deletions, and duplications involving both the p and q arms. We investigated a diagnostically well defined set of 55 t(14;18)-positive FL cases with complex karyotypes by means of multicolor karyotyping. Sixteen cases showed involvement of chromosome 1 and were analyzed in further detail by a novel multicolor banding technique for this chromosome. We defined three groups showing varying complexity of chromosome 1 alterations. The first group revealed simple translocations, such as t(1;2), t(1;6), t(1;8), and t(1;17), involving breakpoints on either the p or the q arm of chromosome 1. The second group showed more complex rearrangements with translocations, insertions, regional duplications, and involvement of more than one partner chromosome with either the p or the q arm of chromosome 1. The third group was defined by highly complex rearrangements involving translocations, regional duplications, amplifications, and intrachromosomal band relocations affecting the entire chromosome 1. All three groups shared interchromosomal rearrangements of chromosome 1 with chromosome 8, often involving the MYC protooncogene site, amplification involving region 1q21-q31, and deletion involving region 1p36. Thus, the use of sophisticated multicolor molecular cytogenetic assays in the investigation of malignant lymphoma allows precise characterization of chromosomal alterations and will provide a better understanding of their biology.     

Comparison of Chemicon SimulFluor direct fluorescent antibody staining with cell culture and shell vial direct immunoperoxidase staining for detection of herpes simplex virus and with cytospin direct immunofluorescence staining for detection of varicella-zoster virus

A new rapid direct immunofluorescence assay, the SimulFluor direct fluorescent-antibody (DFA) assay, which can simultaneously detect herpes simplex virus types 1 and 2 (HSV-1 and -2) and varicella-zoster virus (VZV), was evaluated in comparison with our current standard procedures of (i) shell vial direct immunoperoxidase (shell vial IP) staining and cell culture for detection of HSV and (ii) cytospin DFA staining for VZV detection. A total of 517 vesicular, oral, genital, and skin lesion specimens were tested by all three procedures. For HSV detection, the SimulFluor DFA assay had an overall sensitivity, specificity, positive predictive value, and negative predictive value of 80.0, 98.3, 92.3, and 95.1%, respectively, when compared to culture. Shell vial IP staining had a sensitivity, specificity, positive predictive value, and negative predictive value of 87.6, 100, 100, and 96.9%, respectively, when compared with cell culture. The SimulFluor DFA assay, however, offers same-day, 1.5-hours results versus a 1- to 2-day wait for shell vial IP staining results and a 1- to 6-day wait for culture results for HSV. For VZV detection SimulFluor DFA staining detected 27 positive specimens as compared to 31 by our standard cytospin DFA technique--a correlation of 87.1%. A positive SimulFluor reaction for VZV is indicated by yellow-gold fluorescence compared to the bright apple-green fluorescence observed by cytospin DFA staining. There is no difference in turnaround time between the two assays. The SimulFluor DFA assay is a rapid immunofluorescence assay that can detect 80% of the HSV-positive specimens and 87% of the VZV-positive specimens with a 1.5-h turnaround time.     

Anxiety Treatment and Targeted Sleep Enhancement to Address Sleep Disturbance in Pre/Early Adolescents with Anxiety

Sleep disturbance is prevalent in anxious youth and prospectively predicts poor emotional adjustment in adolescence. Study 1 examined whether anxiety treatment improves subjective and objective sleep disturbance in anxious youth. Study 2 examined whether a sleep intervention called Sleeping TIGERS can further improve sleep following anxiety treatment. Study 1 examined 133 youth (ages 9–14; 56% female; 11% ethnic/racial minority) with generalized, social, or separation anxiety over the course of anxiety treatment (cognitive behavioral treatment or client-centered treatment). Sleep-related problems (parent-, child-report) and subjective (diary) and objective (actigraphy) sleep patterns were assessed across treatment in an open trial design. Study 2 included 50 youth (ages 9–14; 68% female; 10% ethnic/racial minority) who continued to report sleep-related problems after anxiety treatment and enrolled in an open trial of Sleeping TIGERS. Pre- and postassessments duplicated Study 1 and included the Focal Interview of Sleep to assess sleep disturbance. Study 1 demonstrated small reductions in sleep problems and improvements in subjective sleep patterns (diary) across anxiety treatment, but outcomes were not deemed clinically significant, and 75% of youth stayed above clinical cutoff. Study 2 showed clinically significant, large reductions in sleep problems and small changes in some subjective sleep patterns (diary). Anxiety treatment improves, but does not resolve, sleep disturbance in peri-pubertal youth, which may portend risk for poor emotional adjustment and mental health. The open trial provides preliminary support that Sleeping TIGERS can improve sleep in anxious youth to a clinically significant degree.     

Systemic Administration of Immunostimulatory DNA Sequences Mediates Reversible Inhibition of Th2 Responses in a Mouse Model of Asthma

This study investigated whether immunostimulatory DNA sequences (ISS) induce a transient or sustained inhibition of Th2 responses to inhaled antigen. We sensitized mice with subcutaneous injections to develop a Th2 response to ovalbumin (ova) and then administered a dose of ISS prior to ova inhalation challenge. Mice were then rechallenged with ova by inhalation a second time at varying time points after the first ova inhalation (1 to 8 weeks later) to determine whether the ISS dose administered prior to the first ova inhalation protected against a subsequent second ova inhalation challenge. A single dose of ISS inhibited the Th2 response to the first inhalation of ova antigen, as well as 4 weeks later to the second inhalation of ova. However, ISS did not inhibit a Th2 response to the second inhalation of ova 8 weeks later. The reversible inhibition of Th2 responses at 8 weeks suggests the need for repeated ISS administration at monthly intervals.     

Comparison of abilities of recombinant interleukin-1α and -β and noninflammatory IL-1β fragment 163–171 to upregulate C3b receptors (CR1) on human neutrophils and to enhance their phagocytic capacity

Both recombinant IL-1 and - caused an upregulation of C3b receptors (CR1) on human neutrophils and caused a receptor-mediated enhancement of phagocytosis of C3b·IgG-coated microspheres by these leukocytes. The and forms of the recombinant cytokine were of comparable potency regarding CR1 upregulation, although both generally had less than 25% of the potency of FMLP in this respect. Recombinant IL-1 was slightly more potent than the form of the cytokine regarding phagocytosis of opsonized microspheres and, again, both forms were less potent than FMLP in causing an enhancement of phagocytosis by neutrophils. The synthetic noninflammatory immunostimulatory nonapeptide corresponding to residues 163–171 of IL-1 was completely inert with respect to upregulation of CR1 on neutrophils and the enhancement of phagocytosis by these cells. Thus this domain in the intact IL-1 molecule apparently is not involved in CR1 upregulation and the ensuing enhancement in phagocytosis by neutrophils, although it is apparently important in the immunostimulatory activity regarding the proliferation of lymphocytes.     

MR properties of excised neural tissue following experimentally induced demyelination

Changes in the magnetic resonance (MR) parameters of demyelinated neural tissue were measured in vitro using an experimental animal model. A tellurium (Te) diet was applied to weanling rats to induce the demyelination process in the sciatic nerve. The quantitative MR parameters, such as T(1), T(2) relaxation time constants and magnetization transfer (MT) were measured each day after applying the Te diet (up to 7 days) and were found to be substantially different from those of normal nerves. An increase in the average T(1) and T(2) was observed along with a decrease in the MT ratio (MTR) and the quantitative MT parameter M(0B), which describes the semisolid pool of protons. Most of the MR parameters correlated very well with the myelin fraction of neural tissue evaluated by quantitative histopathology. The T(2) relaxation spectrum provided the most efficient quantitative assessment of changes in neural tissue microstructure and its analysis resulted in a powerful tool to distinguish the processes of demyelination and inflammation. In comparison, the MT measurements were less successful.     

Immune responses induced by the Leishmania (Leishmania) donovani A2 antigen,but not by the LACK antigen,are protective against experimental Leishmania (Leishmania) amazonensis infection

Leishmania amazonensis is one of the major etiologic agents of a broad spectrum of clinical forms of leishmaniasis and has a wide geographical distribution in the Americas, which overlaps with the areas of transmission of many other Leishmania species. The LACK and A2 antigens are shared by various Leishmania species. A2 was previously shown to induce a potent Th1 immune response and protection against L. donovani infection in BALB/c mice. LACK is effective against L. major infection, but no significant protection against L. donovani infection was observed, in spite of the induction of a potent Th1 immune response. In an attempt to select candidate antigens for an American leishmaniasis vaccine, we investigated the protective effect of these recombinant antigens (rLACK and rA2) and recombinant interleukin-12 (rIL-12) against L. amazonensis infection in BALB/c mice. As expected, immunization with either rA2-rIL-12 or rLACK-rIL-12 induced a robust Th1 response prior to infection. However, only the BALB/c mice immunized with rA2-rIL-12 were protected against infection. Sustained gamma interferon (IFN-gamma) production, high levels of anti-A2 antibodies, and low levels of parasite-specific antibodies were detected in these mice after infection. In contrast, mice immunized with rLACK-rIL-12 displayed decreased levels of IFN-gamma and high levels of both anti-LACK and parasite-specific antibodies. Curiously, the association between rA2 and rLACK antigens in the same vaccine completely inhibited the rA2-specific IFN-gamma and humoral responses and, consequently, the protective effect of the rA2 antigen against L. amazonensis infection. We concluded that A2, but not LACK, fits the requirements for a safe vaccine against American leishmaniasis.     

On the ERN and the significance of errors

The error-related negativity (ERN) is an event-related brain potential observed when subjects commit errors. To examine whether the ERN is sensitive to the value of errors, the motivational significance of errors was manipulated in two experiments. In Experiment 1, low and high monetary value errors were compared to evaluate the effect of trial value on the ERN. In Experiment 2, subjects performed a flanker task both while their performance was being evaluated and during a control condition. Consistent with the notion that the error-detection system is sensitive to the significance of errors, the ERN was significantly larger on high-value trials in Experiment 1 and during evaluation in Experiment 2. There were no corresponding effects on the correct response negativity, and no behavioral differences between conditions were evident in either experiment. These results are discussed in terms of the functional role of the ERN in response monitoring.