The path from initial inquiry to initiation of treatment for social anxiety disorder in an anxiety disorders specialty clinic

Efficacious treatments for social anxiety disorder have become increasingly available, with approximately three-quarters of treatment completers showing significant improvement [Arch. Gen. Psychiatry 55 (1998) 1133.]. However, very few individuals with social anxiety disorder access these services. The present study reports on the path to initiation of treatment for social anxiety disorder among individuals contacting an anxiety disorder specialty clinic. Of 395 initial telephone inquiries, only 60 individuals (15%) started treatment. Three "critical points" associated with high pretreatment attrition were identified: scheduling an initial interview, attending a scheduled initial interview, and initiating a treatment program after receiving a principal diagnosis of social anxiety disorder. Several demographic variables (e.g., level of education, race) were related to attendance at the initial interview. However, no differences were found between those who did and did not initiate treatment on demographic variables, symptom severity, or quality of life. Given that most individuals who complete treatment for social phobia experience significant benefit, results of the current study suggest that future efforts should be devoted to increasing number of patients who access these services.     

Asphyxia aggravates systemic hypotension but not pulmonary hypertension in piglets with meconium aspiration

Meconium aspiration and birth asphyxia are both separately connected to significant pulmonary and systemic hemodynamic changes in newborns, but, although these insults frequently coexist, their combined effects on the neonatal circulation are still controversial. To determine the pulmonary and systemic circulatory changes induced by pulmonary meconium contamination with concurrent asphyxia, 41 anesthetized and ventilated newborn piglets (10-12 d) were studied for 6 h. Eleven piglets were instilled with a bolus of human meconium intratracheally, and 10 piglets had meconium instillation with immediate induction of an asphyxic insult. Eight piglets had only asphyxia and 12 ventilated piglets served as controls. Meconium instillation (with and without asphyxia) resulted in a sustained decrease in the oxygenation, which remained, however, on the control level in the asphyxic group. Although meconium insufflation (with and without asphyxia) increased pulmonary artery pressure and vascular resistance progressively during the study period, the meconium-induced hypertensive effect was actually diminished by additional asphyxia. Asphyxia alone did not have any effect on these pulmonary hemodynamic parameters. On the other hand, whereas systemic arterial pressure and vascular resistance remained on the control level after meconium instillation alone, asphyxia (with and without pulmonary meconium insult) resulted in a sustained fall in systemic pressure already by 4 h. Our data thus indicate that although the coexisting asphyxia seems to moderate the meconium aspiration-induced pulmonary hypertensive response, this additional asphyxic insult does not affect the associated hypoxemia, but rather significantly exacerbates systemic hypotension.     

Empirically supported treatments in pediatric psychology: where is the diversity?

OBJECTIVE: To examine the extent to which studies used to support empirically supported treatments for asthma, cancer, diabetes, and obesity address issues of cultural diversity. METHOD: We chose original articles (71) of treatments used to support empirically supported treatments (ESTs) published as part of a special series on ESTs in the Journal of Pediatric Psychology. Trained coders reviewed each study to determine if the following were reported: race/ethnicity and socioeconomic status (SES) of the sample, moderating cultural variables, cultural assumptions or biases of the treatment, larger cultural issues, and measurement or procedure bias. RESULTS: Results revealed that few studies addressed cultural variables in any way. Only 27% of the studies reported the race or ethnicity and 18% reported the SES of research participants. Additionally, 6% discussed potential moderating cultural variables. The remaining variables were addressed in 7% or less of the studies. CONCLUSIONS: These data support the criticism that ESTs fail to address important issues of culture and call into question the external validity of ESTs to diverse populations. Future research should explicitly address cultural issues according to the nine recommendations described here.     

Experiences of security associated with pregnancy and childbirth: a study of pregnant women

The aim of this study was to describe the sense of security associated with pregnancy and childbirth and to identify factors associated with it. Security was conceptualized in accordance with Kaufmann as a human need and as a human value. The instrument used was a questionnaire with a 4-point scale. The sample consisted of 481 pregnant Finnish women. The response rate was 69%. Rotated factor analysis was carried out and sum variables were produced. The effects of various background variables were calculated using the Kruskal-Wallis test and the Mann-Whitney U-test. The elements creating security were social support, knowledge, prenatal health-care experiences, support from the partner, livelihood, positive stories and, in multiparae, positive previous childbearing experiences. The most salient finding concerning factors related to security was that women who had no pregnancy-related problems in the current pregnancy reported social support, prenatal health-care experiences and support from the partner as security-creating elements more often than women with such problems. This was the only factor related to manifestation of security. The findings suggest that all pregnant women should be assisted by professionals to find security-creating elements in their particular situation to promote and strengthen the sense of security, paying special attention to women with pregnancy-related problems.     

Reproductive disturbances,pituitary lactotrope adenomas,and mammary gland tumors in transgenic female mice producing high levels of human chorionic gonadotropin

To assess the consequences of prolonged exposure to elevated levels of LH/human chorionic gonadotropin (hCG) in the female, we developed a transgenic (TG) mouse model (hCGbeta+) that overexpresses the hCGbeta-subunit cDNA. Because of the promoter used, ubiquitin C, the transgene is expressed in multiple tissues, including the pituitary gland, in which coupling with the endogenous common alpha-subunit results in synthesis of high levels of bioactive hCG. The TG females presented with precocious puberty, infertility, enhanced ovarian steroidogenesis, and abnormal uterine structure. Pituitary enlargement was evident from the age of 2 months, which progressed to adenomas by the age of 10-12 months. Immunohistochemical studies and electron microscopy demonstrated lactotrope origin for the adenomas, associated with severe hyperprolactinemia. The mammary glands of TG females showed marked lobuloalveolar development followed by mammary tumors with characteristics of adenocarcinoma at the age of 9-12 months. More than 90% of penetrance and high frequency of metastasis (47%) was observed. Formation of the pituitary and mammary gland tumors was totally abolished by ovariectomy despite persistently elevated hCG levels. Taken together, these findings suggest that the hCG-induced aberrations of ovarian function are clearly responsible for the extragonadal tumors observed in these TG mice.     

Prediction of the Oral Absorption of Low-Permeability Drugs Using Small Intestine-Like 2/4/A1 Cell Monolayers

Purpose. To characterize the paracellular route of 2/4/A1 monolayers and to compare the permeabilities of incompletely absorbed oral drugs in 2/4/A1 with those in Caco-2 monolayers. Methods. The cells were cultivated on permeable supports. The 2/4/A1 expression of genes associated with tight junctions was compared with that in the small intestine using RT-PCR. The aqueous pore radii were determined using paracellular marker molecules. The permeabilities of a series of incompletely absorbed drugs (defined as having a fraction absorbed 0 to 80%) after oral administration to humans were studied. Results. Occludin and claudin 1 and 3 were expressed in 2/4/A1. The pore radius of 2/4/A1 was 9.0 ± 0.2 Å, which is similar to that in the human small intestine, although the pore radius was smaller (3.7 ± 0.1 Å) in Caco-2. The relationship between permeability and fraction absorbed of 13 drugs was stronger in 2/4/A1 than in Caco-2. The relationships were used to predict the intestinal absorption of another seven drugs. The prediction was more accurate in 2/4/A1 (RMSE = 15.6%) than in Caco-2 (RMSE = 21.1%). Further, Spearman's rank coefficient between FA and permeability was higher in 2/4/A1. Conclusion. The improved 2/4/A1 cell culture model has a more in vivo-like permeability and predicted the oral absorption of incompletely absorbed drugs better than Caco-2 cells.     

EXO1 variants occur commonly in normal population: evidence against a role in hereditary nonpolyposis colorectal cancer

Mutations in the currently known mismatch repair genes cannot explain all cases of hereditary nonpolyposis colorectal cancer (HNPCC), and novel predisposing genes are actively sought. Recently, mutations in the DNA repair gene EXO1 have been implicated in HNPCC. One truncating and several missense changes were observed in familial colorectal cancer (CRC) cases but not in controls. We evaluated a series of European CRC patients and population controls to clarify whether EXO1 variants may indeed predispose to familial CRC. Several variants observed in patients were also observed in controls with similar frequencies, including the truncating variant proposed previously to be a disease-causing mutation. Thus, little evidence was obtained to support a major causative role of EXO1 in HNPCC, although we cannot exclude a role for EXO1 as a low penetrance cancer susceptibility or modifying gene.     

The interleukin-1 family of cytokines and receptors in human breast cancer: implications for tumor progression

We have previously described the expression of interleukin cytokines (IL)-1alpha, IL-1beta, and IL-1 receptor antagonist (IL-1ra) in human breast cancer (HBC) tissue. Based on our previous studies, we hypothesize that the IL-1 family of cytokines, antagonists (IL-1ra) and receptors (IL-1RI and IL-1RII) are present within the human breast cancer (HBC) tumor microenvironment and that the IL-1 network of cytokines and receptors within the tumor microenvironment can control tumor cell subpopulation expression of other protumorigenic cytokines such as the angiogenic/growth factor, interleukin-8 (IL-8). To test this hypothesis we characterized the in vivo expression of the IL-1 network in HBC tissues and homogenates by immunohistochemistry (IHC) and ELISA. Additionally, we examined IL-1R expression in HBC cell lines in vitro and in a murine xenograft model by IHC. Finally, we determined the ability of IL-1 to induce IL-8 expression in in vitro using HBC cell lines. We observed that not only are the IL-1 cytokines present in HBC tissue and homogenates, but that IL-1Rs and IL-8 are also present in the HBC tumor microenvironment. Additionally, expression levels for some members of the IL-1/IL-8 network of cytokines correlated with the prognostic indicators, ER/PR. Using HBC cell lines, we observed that HBC cell lines express IL-1Rs in vitro and in the xenograft model. Furthermore, in vitro, HBC cell lines show a spectrum of responsiveness to IL-1 as measured by expression the proangiogenic/mitogenic cytokine IL-8. Our data clearly demonstrate the presence and distribution of IL-1 cytokines and receptors in HBC and suggests that the local expression of IL-1 results in the activation of a population of cells within the HBC tumor microenvironment. This activation of the IL-1/IL-1R cytokine family via autocrine and/or paracrine mechanisms leads to a cascade of secondary protumorigenic cytokines. These secondary signals induce the expression of numerous protumorigenic activities such as the expression of IL-8, and subsequently contribute to angiogenesis, tumor proliferation, and tumor invasion.