The orphan receptor CRF2-4 is an essential subunit of the interleukin 10 receptor.

The orphan receptor CRF2-4 is a member of the class II cytokine receptor family (CRF2), which includes the interferon receptors, the interleukin (IL) 10 receptor, and tissue factor. CRFB4, the gene encoding CRF2-4, is located within a gene cluster on human chromosome 21 that comprises three interferon receptor subunits. To elucidate the role of CRF2-4, we disrupted the CRFB4 gene in mice by means of homologous recombination. Mice lacking CRF2-4 show no overt abnormalities, grow normally, and are fertile. CRF2-4 deficient cells are normally responsive to type I and type II interferons, but lack responsiveness to IL-10. By approximately 12 wk of age, the majority of mutant mice raised in a conventional facility developed a chronic colitis and splenomegaly. Thus, CRFB4 mutant mice recapitulate the phenotype of IL-10-deficient mice. These findings suggest that CRF2-4 is essential for IL-10-mediated effects and is a subunit of the IL-10 receptor.

Expressed emotion and psychiatric relapse: a meta-analysis.

BACKGROUND: Expressed emotion (EE) is a measure of the family environment that has been demonstrated to be a reliable psychosocial predictor of relapse in schizophrenia. However, in recent years some prominent nonreplications of the EE-relapse relationship have been published. To more fully address the question of the predictive validity of EE, we conducted a meta-analysis of all available EE and outcome studies in schizophrenia. We also examined the predictive validity of the EE construct for mood disorders and eating disorders. METHODS: An extensive literature search revealed 27 studies of the EE-outcome relationship in schizophrenia. Using meta-analytic procedures, we combined the findings of these investigations to provide an estimate of the effect size associated with the EE-relapse relationship. We also used meta-analysis to provide estimates of the effect sizes associated with EE for mood and eating disorders. RESULTS: The results confirmed that EE is a significant and robust predictor of relapse in schizophrenia. Additional analyses demonstrated that the EE-relapse relationship was strongest for patients with more chronic schizophrenic illness. Interestingly, although the EE construct is most closely associated with research in schizophrenia, the mean effect sizes for EE for both mood disorders and eating disorders were significantly higher than the mean effect size for schizophrenia. CONCLUSION: These findings highlight the importance of EE in the understanding and prevention of relapse in a broad range of psychopathological conditions.

Expressed emotion and clinical outcome in borderline personality disorder.

OBJECTIVE: This longitudinal follow-up study examined the predictive validity of relatives' expressed emotion in a group of patients diagnosed with borderline personality disorder. METHOD: Thirty-five patients with DSM-III-R-diagnosed borderline personality disorder were followed up 1 year after they were discharged from a psychiatric hospital. Clinical outcome was assessed through interviews with patients and their family members. Expressed emotion in the patients' relatives, assessed at the time of the index admission, was then used to predict patients' subsequent clinical outcomes. RESULTS: Contrary to prediction, relatives' criticism and hostility did not predict how well patients did in the year after discharge. Neither did they predict rates of rehospitalization. Clinical outcome was strongly associated with family levels of emotional overinvolvement, however. Patients whose families scored higher on emotional overinvolvement had better clinical outcomes over the course of the follow-up period. CONCLUSIONS: These findings suggest that the association between expressed emotion and patient outcome may be different for patients with borderline personality disorder than it is for patients with schizophrenia or mood disorders.

The relevance of tumour pH to the treatment of malignant disease.

The wide range of tumour pH values that have been determined in human tumours is shown in Fig. 4. It can be seen that tumour pH values may be very low, or may fall in the same range as the values found in normal tissues. This means that pH-mediated modification of therapeutic effectiveness will be patient specific, rather than a general phenomenon. That the pH of the cellular environment might influence the effectiveness of various therapeutic agents is not a new idea. The data published in this field to date concerning such effects have been discussed extensively and are summarized in Table IV. Here we can see that low pH leads to decreased cell survival following treatment with hyperthermia, radiotherapy combined with hyperthermia, radiosensitizers and various chemotherapeutic agents. Conversely, low pH affords some protection against radiation and some drugs. Most of these data were, of necessity, derived from in vitro studies. In vivo studies are in most cases not feasible due to the difficulty of isolating the effect of one selected factor. Low tumour pH is, in vivo, generally assumed to be closely interlinked with tissue hypoxia and low blood-flow levels, each of which may individually influence the experimental outcome. Moreover, most of the aforementioned in vitro studies were conducted under well-oxygenated conditions. As previously mentioned, euoxic cells can, under certain conditions, maintain a pH gradient over the cell membrane. This collapses with the onset of hypoxia, leading to intracellular acidification. Low oxygen levels have been shown to be characteristic of many tumours. Within these limitations it is thus evident that tumour pH values could have far-reaching consequences for therapy. If the in vitro findings should prove to be relevant to the clinical situation various applications are possible. Pre-selection of patients less likely to respond to certain (toxic) chemotherapeutic agents, or conversely selection of agents that are more likely to be effective in the pH range of the tumour to be treated are two examples. Alternatively, the exploitation of low tumour pH values is a possibility. Agents that form or release toxic derivatives in areas of low pH, e.g., pH-sensitive liposomes, will work selectively in such areas. Tumour selective therapy may also be possible in patients with higher tumour pH values if the tumour pH can be lowered. This has been achieved experimentally by the administration of hyperthermia at temperatures above 42 degrees C, or by the administration of glucose.(ABSTRACT TRUNCATED AT 400 WORDS)

Pain insensitivity in the relatives of schizophrenia patients.

The psychiatric literature contains anecdotal reports of diminished pain sensitivity in schizophrenia that date back to Kraepelin. Yet, the phenomenon of pain insensitivity in schizophrenia remains largely unstudied. For example, it is not clear if pain insensitivity is a consequence of the illness or if it is also present in the well relatives of schizophrenia patients. To explore this issue, we examined pain thresholds and pain tolerances in healthy young adults. Compared with controls with no family history of psychopathology (n=21), participants with a family history of schizophrenia (n=32) showed elevated pain thresholds and pain tolerances to finger pressure. Pain insensitivity was also significantly correlated with elevated scores on measures of self-referential thinking, magical ideation, and perceptual disturbances. Finally, a sizeable minority (19%) of well relatives of schizophrenia patients showed extreme pain insensitivity compared to other participants. The pattern of findings suggests that pain insensitivity may warrant further exploration as a potential marker of underlying liability to psychosis.

Elevated levels of cognitive-perceptual deficits in individuals with a family history of schizophrenia spectrum disorders.

This study finds that the relatives of schizophrenics have elevated scores on the cognitive-perceptual factor of the schizotypal personality questionnaire (SPQ), particularly for the 'unusual perceptual experiences' and 'ideas of reference' subscales. These results support recent findings by Kremen et al. (1998) and suggest that previous failures to demonstrate elevated scores on 'positive' symptoms of schizotypy may be a function of instrumentation.

Expressed emotion and relapse in alcoholic patients.

Although family members' expressed emotion (EE) predicts patients' elevated relapse rates in schizophrenia and mood disorders, little is known about the relationship between EE and relapse in alcoholism. For 86 alcoholic patients (78 men, 8 women), the association between the spouse's EE and the alcoholic patient's subsequent relapse status in the 12 months after the couple began an outpatient behavioral marital therapy (BMT) program for alcoholism was examined. Alcoholic patients with high EE spouses, when compared with their counterparts with low EE spouses, were more likely to relapse, had a shorter time to relapse, and drank on a greater percentage of days in the 12 months after starting BMT. EE continued to be associated with relapse after patients' age, education, and alcohol problem severity were taken into account. Greater use of Antabuse and more sessions of BMT were associated with reduced relapse for alcoholic patients with high EE spouses.

Allure of self-confirmation: a comment on Swann, Wenzlaff, Krull, and Pelham.

Swann, Wenzlaff, Krull, and Pelham (1992) described the results of 4 studies designed to examine the relation of depression and negative feedback seeking. Unfortunately, problems of the characterization of subjects and of constructs, as well as the interpretation of data trends, combine to limit the conclusions that can be drawn from these studies. We provide a brief review of these problems.

Predictors of relapse in unipolar depressives: expressed emotion, marital distress, and perceived criticism.

The predictive validity of expressed emotion (EE) and two conceptually related but more easily measured alternatives--marital distress, and patients' perceptions of criticism from spouses--were examined in a sample of hospitalized unipolar depressives. All three psychosocial variables were significantly associated with 9-month relapse rates. Expressed emotion and marital distress predicted the same proportion of variance in patients' outcomes. The single best predictor of relapse, however, was a patient's response to the question "How critical is your spouse of you?" Patients who relapsed rated their spouses as significantly more critical than did patients who remained well. Alone, the perceived criticism variable accounted for more of the variance in relapse rates than that explained by EE and marital distress combined. The results suggest that asking depressed patients how critical they believe their relatives are may facilitate the identification of individuals at high risk for relapse subsequent to hospital discharge.

Alternative measures of expressed emotion: a methodological and cautionary note.

Undergraduate raters listened to Camberwell Family Interviews that had been conducted with the spouses of depressed patients and then rated each relative with a rating-scale assessment of expressed emotion (EE). Students' ratings of relatives' criticism, hostility, emotional overinvolvement, and warmth were significantly correlated with trained raters' EE assessments obtained in the conventional manner. Despite this correspondence, further analyses revealed that undergraduates' assessments of relatives did not predict 9-month relapse rates in patients. These results highlight the importance of establishing both the concurrent and predictive validity of any alternative measure of EE. They also emphasize the dangers of assuming that significant correlates of EE are necessarily significant predictors of relapse.

Directed forgetting of emotional stimuli in borderline personality disorder.

On the basis of clinical literature, the authors hypothesized that individuals with borderline personality disorder (BPD) would show biased information processing when they were exposed to negative affective stimuli of a particular type. Individuals with BPD and controls were tested using a directed forgetting paradigm. Study participants were exposed to 3 types of words (borderline, neutral, positive) and were cued to either remember or forget each word as it was presented. There were no group differences on a free recall task for words in the remember condition. However, participants with BPD recalled significantly more of the borderline words from the forget condition than did controls. In other words, borderline participants remembered borderline words that they were instructed to forget. These results may be consistent with enhanced encoding of salient words and perhaps related themes in BPD individuals.

Expressed emotion and causal attributions in the spouses of depressed patients.

High levels of expressed emotion are thought to be related to the attributions relatives make about the causes of a patient's illness and problem behaviors. Causal attributions occurring during spontaneous speech in 43 spouses of depressed patients were examined. Consistent with theoretical prediction and with previous research in schizophrenia, high critical spouses were more likely than low critical spouses to attribute patients' symptoms and negative behaviors to factors that were controllable by and personal to the patients. High critical spouses also made more attributions that implied that they held patients responsible for their difficulties. Although predictive of spouses' criticism, these attribution dimensions did not predict patient relapse. The results suggest that causal attributions are important for understanding spouses' criticism but are of limited predictive validity with respect to depressive relapse.

Personality and expressed emotion.

Expressed emotion (EE) is an established psychosocial predictor of relapse in patients with schizophrenia and mood disorders; however, nothing is currently known about the personality characteristics of high- and low-EE relatives. A total of 45 relatives of schizophrenia patients completed the California Psychological Inventory, a widely used measure of common personality traits. Compared with low-EE relatives, high-EE relatives were more conventional in their behavior (higher norm-favoring) and less satisfied with themselves and their lives (lower self-realization). High-EE relatives were also less flexible, tolerant, and lower in empathy and achievement via independence than were low-EE relatives. Even with statistical control of potential demographic confounds, flexibility remained a significant predictor of EE status.

Clinically derived dose effect relationship for hyperthermia given in combination with low dose radiotherapy.

A group of 36 patients, treated on 44 fields with fractionated treatments of local high-frequency induced hyperthermia and radiotherapy to the low total dose of 14-25 Gy, was retrospectively evaluated for differences between responders (i.e., complete and partial responders) and non-responders. A response rate of 86% was achieved, comprising 14% (6/44) complete and 73% (32/44) partial response. There was an indication that the probability of complete response is greater in smaller tumours. The tumour temperatures achieved were higher in the responders than in the non-responders. Logistic analysis was performed on the mean temperature achieved. This temperature parameter yielded a significant positive dose-effect relationship with regard to therapeutic effect, from which a 50% effective dose of 38.8 degrees C was calculated. The data indicate that to obtain the maximum therapeutic effect, i.e., greater than 95% response rate, tumour temperatures above 42.5 degrees C need to be achieved.

The effect of polylactic acid granules on the incidence of alveolar osteitis after mandibular third molar surgery. A prospective randomized study.

OBJECTIVE: To evaluate the effect of polylactic acid granules placed in third molar sockets on the incidence of alveolar osteitis. STUDY DESIGN: A prospective randomized study with 161 patients (322 bilaterally impacted mandibular third molars). RESULTS: The sockets in which the polylactic acid granules were placed had a significantly higher rate of alveolar osteitis (23.6%) than did the control sockets (13.58%). In all subgroups analyzed, the incidence of alveolar osteitis was higher in the experimental (polylactic acid) group. CONCLUSION: On the basis of the findings of this study, polylactic acid granules do not reduce the incidence of alveolar osteitis and may actually contribute to a higher incidence of alveolar osteitis.

Predicting expressed emotion: a study with families of obsessive-compulsive and agoraphobic outpatients.

The authors used structural equation modeling to examine expressed emotion (EE) in relatives of outpatients with panic disorder with agoraphobia (n = 42) or obsessive-compulsive disorder (n = 60). EE was examined as a function of patients' illness and personality and as a function of characteristics of relatives themselves. EE was operationalized in terms of hostility on the Camberwell Family Interview (C. E. Vaughn & J. P. Leff, 1976) and patients' ratings of their relatives' criticism (perceived criticism). Key findings include the identification of a characteristic of the relative (self-reported angry thoughts, feelings, and behaviors) that is directly linked to both hostility toward the patient and to perceived criticism, as well as a direct path between relatives' low rates of observed problem solving and their hostility toward the patient. Patient Pathology predicted perceived criticism but not observer-rated hostility.

Surgical extractions.

The principles of exodontia as they pertain to surgical extractions are presented in this article. A system of presurgical analysis that will alert the dentist to potential problems is outlined. Also, classic techniques of surgical extractions and root retrieval are presented.

Oral mucosal biopsy procedures. Excisional and incisional.

Incisional and excisional biopsies of oral mucosal lesions are procedures the dental practitioner should employ for total patient care. Indications and contraindications for obtaining biopsy specimens are outlined in this article. Also, basic and adjunctive surgical techniques are described with an emphasis on a continuum of care until resolution.

Developing family psychoeducational treatments for patients with bipolar and other severe psychiatric disorders. A pathway from basic research to clinical trials.

Developing family treatments for patients with severe and persistent psychiatric disorder begins at the basic research level, through identifying psychosocial variables that have prognostic significance. Treatment protocols informed by this basic research can then be designed, manualized, and piloted. Next, the efficacy of a new treatment is examined, first in a randomized trial and then, if successful, in a community effectiveness study. We describe this treatment development pathway in a population for whom family attributes have prognostic importance: patients with bipolar affective disorder. The methodological complexities of psychosocial treatment studies are many. Moreover, the results of these studies often reflect interactions between treatment, process, and outcome variables.