The Research Directions Survey: patient and parent perspectives of eating disorder research.

Seventy-two patients and parents completed the "Research Directions Survey" (RDS), consisting of an open-ended question and four rank-ordered lists. The RDS was designed to examine aspects of eating disorders (ED) that these individuals perceive as priorities for future research. The top three themes emerging from the open-ended question were treatment, family dynamics, and motivation for recovery. In the four ranking questions, respondents indicated low self-esteem, weight-related comments, body image distortions, and individual psychotherapy as most important for future research. This paper discusses the implications of our findings and directions for future research in ED.

Information as a distinct dimension for satisfaction assessment of outpatient psychiatric services.

The purpose of this study is to verify whether information on services would appear as a distinct dimension of satisfaction in a multidimensional scale. Data collection was performed in two phases: 263 patients received the original version of the questionnaire and 200 received an adapted version of the scale. The findings suggest that not only is it important to consider information as a distinct dimension of satisfaction but it is equally important to examine three categories, consisting of satisfaction with information on; patients' problems/illness; distinct treatment components such as medication and psychotherapy; and patients' treatment progress.

High-dose therapy with 90Yttrium-labeled monoclonal antibody CC49: a phase I trial.

A Phase I trial of increasing administered activities of 90yttrium (90Y)-labeled monoclonal antibody (MAb) CC49 was conducted to determine whether extrahematopoietic toxicity occurred with this radioimmunoconjugate. Twelve patients with various gastrointestinal tract cancers were administered a tracer dose of 111In-labeled MAb CC49 for biodistribution and pharmacokinetic studies. Patients then underwent a single treatment with increasing administered activities of 90Y-labeled MAb CC49 (0.3, 0.4, and 0.5 mCi/kg). Biodistribution studies, using 111In-labeled MAb CC49 as a surrogate, were determined using planar and single photon emission computed tomography imaging. Pharmacokinetic studies were performed by measuring radioactivity in blood samples taken at intervals after radioimmunoconjugate infusions. Tissue biopsies of tumor metastases and related normal tissues (liver and bone marrow) were obtained for radioactivity measurements. Radiation dosimetry estimates were calculated using these data. Toxicity was evaluated using the National Cancer Institute Common Toxicity Criteria. No dose limiting extrahematopoietic toxicity was identified in the range of administered activities used in this study. Radioimmunolocalization based on planar and single photon emission computed tomography images 111In-labeled MAb CC49 showed heterogeneous (nonspecific) liver and splenic uptake. Liver metastases were usually photopenic, and extrahepatic metastases showed faint to moderate uptake. The alpha and beta half-lives of 111In-labeled MAb CC49 and 90Y-labeled MAb CC49 in the blood were similar. Absorbed radiation dose estimates in metastatic tumor sites ranged from 180 to 3000 cGy. The percentage of injected dose/kg of tumor ranged from 1.12 to 18.14; however, tumor:normal liver ratios were consistently <1. No objective responses were observed. Doses of up to 0.5 mCi/kg could be administered with reversible grade IV myelotoxicity. Absorbed radiation dose in tumor was suboptimal, even at the highest administered activity level. Deposition of 90Y in liver was high, and estimates of absorbed dose in liver equaled or exceeded that which could be achieved in metastatic tumor sites. Strategies to enhance access of radioimmunoconjugates in tumor and diminish deposition in the liver need to be developed for effective treatment using MAb CC49 with chelated radiometals.

Phase I/II trial of multiple dose 131Iodine-MAb LL2 (CD22) in patients with recurrent non-Hodgkin's lymphoma.

The purpose of this to evaluate in a phase I/II study the efficacy and toxicity of a multi-dose administration of 131I labeled CD22 monoclonal antibody (131I-MAb-LL2) in escalating dose cohorts administered to relapsed non-Hodgkin's lymphoma (NHL) patients. Twenty-one patients with relapsed NHL received one of four dose levels of 131-MAb-LL2 administered in a twice weekly pattern. Starting with dose level 2, the patients also received 20 mg of unlabeled LL2 prior to each radiolabeled dose administered. Previously stored autologous peripheral blood progenitors were reinfused in case of prolonged cytopenias. Patients could repeat the same treatment if they had stable disease or a response to the first therapy at 8 weeks, and had not received their peripheral blood progenitors with the first cycle. Combining all of the dose cohorts, there were 5 complete responses or complete responses (undetermined) and 2 partial responses for a total response rate of 7/21 (33%). There was no dose response effect with responses documented at all dose levels. Expected toxicities were hematopoietic, requiring stem cell re-infusion in 5 patients. Other toxicities included hypothyroidism in 3 patients, and human anti-mouse antibody formation (HAMA) in 4 patients. In conclusion, 131I-MAb-LL2, when administered in a multi-dose fashion with 20 mg unlabeled antibody pre-dosing, resulted in a response rate of 33% in heavily pre-treated NHL patients. Non-hematologic toxicities were mild and few in number. Further evaluation of this treatment is warranted and further dose escalation will be possible.

Family climates: family factors specific to disturbed eating and bulimia nervosa.

More than a decade of research has characterized the families of individuals with bulimia and bulimia anorexia (Anorexia Nervosa, Binge/Purging Type) as less expressive, less cohesive, and experiencing more conflicts than normal control families. This two-part study investigated variables believed more directly related to disturbed eating and bulimia as contributing to a "family climate for eating disorders." In Study 1. a nonclinical sample of 324 women who had just left home for college and a sample of 121 mothers evaluated their families. Principal-components analyses revealed the same factor structure for both students and mothers, with Family Body Satisfaction, Family Social Appearance Orientation, and Family Achievement Emphasis loading together, representing the hypothesized family climate for eating disorders: the remaining variables loaded with the more traditional family process variables (conflict, cohesion, expressiveness), representing a more general family dysfunction. As predicted, the family climate for eating disorders factor score was a more powerful predictor of disturbed eating. Study 2 extended these findings into a clin ical population, examining whether the family climate for eating disorders variables would distinguish individuals with bulimia from both depressed and healthy controls. Groups of eating-disordered patients (n = 40) and depressed (n = 17) and healthy (n = 27) controls completed family measures. The eating-disordered group scored significantly higher on family climate variables than control groups. Family process variables distinguished clinical groups (depressed and eating disordered) from healthy controls, but not from one another. Controlling for depression removed group differences on family process variables, but family climate variables continued to distinguish the eating-disordered group from both control groups. Indications for further research are discussed.

Psychiatric residents' views on their training and experience regarding issues related to child abuse.

OBJECTIVE: To explore the views of psychiatric residents regarding the prevalence and impact of child physical, sexual, and emotional abuse; the adequacy of their training in these areas; and the sufficiency of treatment resources for abused children and their abusers. METHOD: A 97-item survey questionnaire was distributed to 189 psychiatric residents as a section of the 1997 Coordinators of Postgraduate Education (COPE) self-assessment examination. RESULTS: Estimations of prevalence of child sexual, physical, and emotional abuse among men and women in both general and psychiatric populations were generally accurate according to the literature. Residents appeared to be aware of the multifactorial nature of child abuse and identified the particular importance of social-environmental factors such as parental drug abuse and a violent social environment. Residents also recognized the significant association of posttraumatic stress disorder, borderline personality disorder, and dissociative disorders with child sexual abuse. Seventy-five percent of respondents felt that instruction on the topic of child abuse during their psychiatric residency was insufficient. Sixty-four percent of respondents felt that resources for the treatment of effects of child abuse were insufficient; 83% felt that treatment resources for child abusers were insufficient. CONCLUSION: Although psychiatric residents appear to be aware of the prevalence of child abuse and its varied effects on the victims' mental health, the majority felt that their medical training in this area had been insufficient. For this reason, medical school curricula and training experiences might require reevaluation. Increasing the profile of child abuse and its impact on mental health might also result in enhanced prevention programs and treatment resources available to abused children and their abusers.

High-dose therapy with iodine-131-labeled monoclonal antibody CC49 in patients with gastrointestinal cancers: a phase I trial.

PURPOSE: A phase I trial that evaluated for extrahematopoietic toxicity was conducted with iodine-131 (131I) labeled monoclonal antibody (MAb) CC49. Correlative studies included pharmacokinetic and biodistribution analyses, estimates of absorbed radiation dose, and measurement of human antimonoclonal antibodies (HAMA). PATIENTS AND METHODS: After collection and cryopreservation of hematopoietic stem cells, 15 patients with gastrointestinal cancers were administered a tracer dose of 131I-MAb CC49. Within 5 to 6 days, 14 patients (two to three per activity level) underwent a single treatment with 131I-MAb CC49 (50, 100, 150, 200, 250, and 300 mCi/m2). Biodistribution was determined using planar and single photon emission computer tomographic (SPECT) imaging. Pharmacokinetic studies were performed by measuring radioactivity in serial blood samples. In some patients, biopsies of metastases and related normal tissues were obtained for radioactivity measurements. Radiation dosimetry estimates were calculated using available biodistribution, pharmacokinetic, and tissue biopsy data. Toxicity was evaluated using the National Cancer Institute (NCI) Common Toxicity Criteria. RESULTS: No dose-limiting extrahematopoietic toxicity was identified. Twelve patients experienced grade IV myelosuppression and met criteria for infusion of hematopoietic stem cells. Radioimmunolocalization was excellent. The T1/2 for 131I-MAb CC49 after diagnostic and therapeutic administration was 39.7 +/- 10.4 and 46.1 +/- 10.6 hours, respectively. The percent injected dose per killigram of tumor ranged from 0.2 to 2.1. Absorbed radiation dose in metastatic tumor sites ranged from 630 to 3300 cGy. CONCLUSION: Although extrahematopoietic dose-limiting toxicity was neither observed or predicted, suboptimal absorbed dose estimates suggested that further escalation of 131I-MAb CC49 would not be useful. Future studies should focus on the use of radionuclides with high energy beta emissions, such as yttrium 90, and on strategies to optimize access of antibody to target antigens.

Patient-specific dosimetry of indium-111- and yttrium-90-labeled monoclonal antibody CC49.

UNLABELLED: The objective of this work was to develop patient-specific dosimetry for patients with metastatic gastrointestinal tract cancers who received 111In-CC49 IgG for imaging before therapy with 90Y-CC49 IgG. METHODS: Whole-body imaging of 12 patients, who received 111-185 MBq (3-5 mCi) of 111In-CC49, commenced in < 2 hr postinfusion and was continued daily for 4-5 days. SPECT data were acquired at 24 and 72 hr to determine the range of 111In-CC49 activity concentrations in tumors and normal organs. Time-activity curves were generated from the image data and scaled from 111In-CC49 to 90Y-CC49 for dosimetric purposes. Absorbed-dose calculations for 90Y-CC49 included the mean and range in tumor and normal organs. Computed 90Y-CC49 activity concentrations were compared with measurements on 10 needle biopsies of normal liver and four tumor biopsies. RESULTS: In 9 of 10 normal liver samples, the range of computed 90Y-CC49 activity concentrations bracketed measured values. This was also the case for 3 of 4 tumor biopsies. Absorbed-dose calculations for 90Y-CC49 were based on patients' images and activities in tissue samples and, hence, were patient-specific. CONCLUSION: For the radiolabeled antibody preparations used in this study, quantitative imaging of 111In-CC49 provided the data required for 90Y-CC49 dosimetry. The range of activities in patients' SPECT images was determined for a meaningful comparison of measured and computed values. Knowledge of activity distributions in tumors and normal organs was essential for computing mean values and ranges of absorbed dose and provided a more complete description of the absorbed dose from 90Y-CC49 than was possible with planar methods.

Patient-specific dosimetry using quantitative SPECT imaging and three-dimensional discrete Fourier transform convolution.

UNLABELLED: The objective of this study was to develop a three-dimensional discrete Fourier transform (3D-DFT) convolution method to perform the dosimetry for 131I-labeled antibodies in soft tissues. METHODS: Mathematical and physical phantoms were used to compare 3D-DFT with Monte Carlo transport (MCT) calculations based on the EGS4 code. The mathematical and physical phantoms consisted of a sphere and a cylinder, respectively, containing uniform and non-uniform activity distributions. Quantitative SPECT reconstruction was carried out using the circular harmonic transform (CHT) algorithm. RESULTS: The radial dose profile obtained from MCT calculations and the 3D-DFT convolution method for the mathematical phantom were in close agreement. The root mean square error (RMSE) for the two methods was < 0.1%, with a maximum difference < 21%. Results obtained for the physical phantom gave a RMSE < 0.1% and a maximum difference of < 13%; isodose contours were in good agreement. SPECT data for two patients who had undergone 131I radioimmunotherapy (RIT) were used to compare absorbed-dose rates and isodose rate contours with the two methods of calculation. This yielded a RMSE < 0.02% and a maximum difference of < 13%. CONCLUSION: Our results showed that the 3D-DFT convolution method compared well with MCT calculations. The 3D-DFT approach is computationally much more efficient and, hence, the method of choice. This method is patient-specific and applicable to the dosimetry of soft-tissue tumors and normal organs. It can be implemented on personal computers.

Antiidiotypic response against murine monoclonal antibodies reactive with tumor-associated antigen TAG-72.

The immune response of 42 gastrointestinal and ovarian cancer patients at 1 month after exposure to murine monoclonal antibodies (B72.3 and CC49) reactive with the tumor-associated antigen TAG-72 was studied. The incidence of human anti-mouse antibody response was 89% to B72.3 and 70% to CC49. To evaluate the antiidiotypic immune response, we developed a serological assay based on affinity chromatography to remove the interference due to the presence of TAG-72, antiisotypic, and antiallotypic immunoglobulins in the serum. Seventy-eight percent of patients who received B72.3 developed an antiidiotypic response; in 33% of the patients, this was the only immune response detected. The antiidiotypic immune response after treatment with CC49 was present in 54% of the patients. Twelve percent of the patients who received CC49 developed an antiidiotypic response in the absence of antiisotypic or antiallotypic immune response. The lower immunogenicity of the variable region of CC49 is encouraging when considering the use of chimeric or humanized antibodies derived from the murine monoclonal antibody CC49 in clinical studies.

[The future of psychiatric hospitals in Ontario]. / L'avenir des hôpitaux psychiatriques en Ontario.

The purpose of this paper is to review past and present roles and to speculate on the future of the Ontario provincial psychiatric hospitals (PPHs). Currently, and for the very immediate future only, there are 10 PPHs that are owned and operated by the Ministry of Health of Ontario, each serving a specified population ranging from 250,000 to over 3,000,000. In addition to clinical expertise, provincial psychiatric hospitals contribute greatly to teaching and research. Ontario's mental health reform movement has called for a shift of resources to the community and a downsizing of PPHs by 2003. In response to fiscal pressures, in 1996 provincial legislation was passed to establish the Health Services Restructuring Commission (HSRC) as a stand-alone corporation with powers to restructure and reengineer health services in Ontario. The HSRC has to date recommended the closure of 4 PPHs by 1999 and the integration of theses services into other medical facilities. While a rebalancing of the mental health system does need to take place, the fiscally driven haste to close hospitals has created a crisis atmosphere in PPHs for staff and patients. It is also unlikely that the necessary community resources will be in place to buffer these changes. The new restructuring plans not only set unrealistic timelines, they seem to underestimate the importance PPHs have played in teaching, research and the advancement of clinical treatment and rehabilitation of the severely mentally ill. It may be that, in the long run, service integration and divestment/closure of the PPHs will result in better access to services closer to smaller communities and in the destigmatization of the mentally ill, however, without close evaluative monitoring and appropriate leadership, it could also lead to decreased research, training and quality of care.

Radiolabeled iododeoxyuridine: safety evaluation.

UNLABELLED: The emphasis of radiolabeled iododeoxyuridine (*IUdR) research at our institution to date has been to assess its safety as a potential therapeutic agent. Toward this goal, we have performed preclinical and clinical studies, using various routes of administration, to detect adverse changes in normal tissues in both humans and animals. As IUdR is rapidly dehalogenated by the liver, the intravenous route is unlikely to be successful in therapeutic efforts. We have therefore focused our attention on more "protected" routes: intra-arterial and intravesicular administration. METHODS: Studies were performed in farm pigs after multiple administrations of [125I]IUdR into the aorta, carotid artery and bladder. IUdR and metabolites were measured in venous blood samples at appropriate time intervals after administration, after which histologic examination of tissues was performed. Studies in human have been performed after intra-arterial administration of [123I]IUdR in patients with liver metastases and intravesicular administration in patients with bladder carcinoma, initially using [123I]IUdR and currently using both [123I]IUdR and [125I]IUdR. Blood samples for pharmacokinetics and metabolite analysis and tissue for autoradiography (when feasible) have been obtained. RESULTS: To date, no evidence of adverse effects on normal tissue or alteration of hematologic or metabolic indices have been seen in pigs or humans. When instilled in the bladder, there is little leakage of IUdR in the circulation. CONCLUSION: When [125I]IUdR is used as a therapeutic agent, we anticipate little or no effect on normal tissues.

Patients' requests and satisfaction with services in an outpatient psychiatric setting.

OBJECTIVE: Patients in four major diagnostic categories were compared to determine if their satisfaction with outpatient services varied. Both overall satisfaction and the degree to which clients and therapists agreed on the importance of 16 aspects of treatment were examined. METHODS: The Patient Request Form (PRF) and the Client Satisfaction Questionnaire were used to interview 464 outpatients. The professional who was the primary contact for each patient filled out a therapist version of the PRF. Diagnoses were grouped into four major categories: anxiety disorders, affective disorders, schizophrenia, and other psychotic disorders. RESULTS: The diagnostic groups differed in overall satisfaction with treatment, treatment characteristics, patients' reasons for coming to the clinic, therapists' descriptions of treatment, and patient-therapist agreement on the importance of different aspects of treatment. Agreement between patients and providers was associated with higher levels of patients' satisfaction. Patients with schizophrenia or with other psychotic disorders had the lowest level of agreement with their therapists and also were the least satisfied. In all patient categories, therapists underestimated the importance to patients of having a reliable source of help. CONCLUSIONS: The greater dissatisfaction expressed by patients with schizophrenia and other psychotic disorders may be related to their therapists' undervaluing the nonbiological aspects of treatment such as social support. Combining medication with psychosocial approaches that have been adapted for patients with psychotic disorders is likely to improve the patients' satisfaction and compliance and increase the overall effectiveness of treatment.

Survival of patients with resistant Hodgkin's disease after polyclonal yttrium 90-labeled antiferritin treatment.

PURPOSE: A follow-up study was initiated of patients with Hodgkin's disease who were treated with yttrium 90-labeled antiferritin. Prescription method, pharmacokinetics, acute and late side effects, and survival were evaluated. METHODS: Patients had measurable disease and failed > or = two multiagent chemotherapy regimens previously (N = 44). All patients received 5-mCi indium 111-labeled antiferritin 2 mg intravenously and were scanned repeatedly by gamma camera. In five patients, polyclonal antiferritin (rabbit, pig, or baboon) failed to target the tumor. Thirty-nine patients were injected intravenously with 10-, 20-, 30-, 40-, or 50-mCi yttrium 90-labeled antiferritin 2 to 5 mg. Patients received between one and five cycles. Some patients were supported with 5 x 10(7) autologous bone marrow cells per kilogram. RESULTS: Yttrium 90-labeled polyclonal antiferritin does not produce immunologic, pharmacologic, or microbiologic complications in vivo. Bone marrow toxicity is the only side effect observed. Overall response rate is 20 of 39, or 51%. Two patients had stable disease. A significant positive correlation is found between blood radioactivity level 1 hour after radioimmunoconjugate administration and subsequent response of Hodgkin's disease. A dosage in millicuries per kilogram provides a higher positive correlation with blood radioactivity levels 1 hour after administration than a dosage in millicuries per square meter of body-surface area or in total millicuries. Fifty percent of patients survive for > or = 6 months. CONCLUSION: The low-dose protein used (2 to 5 mg) indicates that the high response rate is due to radiation and not to immunologic effects of the antibody. High-activity administrations followed by bone marrow transplantation are not required for tumor response. The therapeutic ratio of radiolabeled antiferritin is higher than the therapeutic ratio observed in most phase I studies of chemotherapeutic agents. This analysis does not identify a superior mode of treatment for patients with end-stage Hodgkin's disease. However, in a heavily pretreated patient population, prolonged survival is observed after relatively inexpensive treatment. Preclinical research with yttrium 90-labeled antiferritin indicates that significant increases in tumor dose can be obtained in the future without an increase in normal tissue toxicity.

SPECT imaging of fluorine-18.

UNLABELLED: The objective of this work was to determine the potential clinical usefulness of SPECT to image 511-keV annihilation photons. METHODS: A triple-headed gamma camera equipped with ultra-high-energy collimators was used to image 18F. Sensitivity measurements were carried out and the FWHM and FWTM were determined in air and for a unit-density scattering medium. Additionally, tomographic phantom studies were acquired to evaluate image quality. RESULTS: The sensitivities of the three cameras were, for all practical purposes, identical. At a source-to-collimator distance of 100 mm, the FWHM and FWTM were 13 and 29 mm, respectively. A tomographic phantom study demonstrated that spheres with a diameter of 20 mm were well resolved when filled with 18F activity and placed inside a water-filled phantom. CONCLUSION: The triple-headed SPECT camera in this investigation is a practical means of acquiring tomographic 18F images. The reconstructed slices were of sufficient quality to be of value in some clinical studies.

Prevalence of dissociative symptoms and disorders in an adult psychiatric inpatient population in Canada.

OBJECTIVE: This study attempted to estimate the prevalence of dissociative symptoms and disorders in a Canadian adult psychiatric inpatient population and also attempted to determine the extent to which dissociative disorders were recognized by the attending clinical staff. METHOD: All appropriate and consenting adult psychiatric inpatients at the Kingston Psychiatric Hospital in Kingston, Ontario, were given the Dissociative Experiences Scale. Patients scoring 25 or greater were interviewed with the Dissociative Disorders Interview Schedule and the Structured Clinical Interview for DSM-IV Dissociative Disorders. Admission or discharge diagnoses data were used to determine whether or not dissociative disorders were being recognized. RESULTS: A total of 48 patients completed the Dissociative Experiences Scale and 14 (29%) scored 25 or greater. The prevalence of dissociative disorders in this hospital population was estimated to be 17%. Dissociative identity disorder was found in six percent, dissociative amnesia in eight percent and dissociative disorder not otherwise specified in two percent of the population. These disorders tended to be under-recognized. CONCLUSION: Research on more extensive populations is required to establish the true prevalence of dissociative symptoms and disorders in psychiatric inpatients.

Residents' perceptions of transcultural psychiatric practice.

A questionnaire was distributed to 190 psychiatry residents to analyze the impact of three factors on residents' perceptions of their transcultural practice: cultural identity of residents; degree of exposure to patients from different cultures; and training in cultural psychiatry. Results suggest that residents' perceptions vary according to the resident's cultural origin. The training in psychiatry and the degree of exposure to patients from different cultures had no significant influence on the residents' perceptions. Overall these results emphasize the necessity to revise the cultural content of residents' psychiatry curriculum to, among other things, raise residents' awareness of their own cultural identity.

A unified approach to photon and beta particle dosimetry.

UNLABELLED: The purpose of this investigation was to develop a unified and practical method for photon and beta particle dosimetry. METHODS: This was achieved by developing a point-source function that is equally valid for photons and beta particles. This function contains four fitting parameters. These were computed on the basis of Berger's tables for a wide range of photon and beta particle energies. Explicit formulas were derived for the absorbed fraction within and outside of spheres containing a uniform distribution of activity. For photons, calculations of the absorbed fraction at the center of spheres were compared with the results of Monte Carlo calculations. The two methods yielded essentially identical results, validating the approach used in this study. RESULTS: The results of this study show that there are absorbed-dose gradients as a function of distance from the center of a sphere. These should be taken into account in absorbed-dose calculations. For beta particles, it is shown explicitly that for spheres with a radius of 0.08 cm, absorbed-dose rates from 131I and 90Y beta particles are equal. CONCLUSION: An important feature of this work is that calculations can be made on the macroscopic, cellular and subcellular levels. The approach employed and results obtained in this work should be particularly useful for tumor dosimetry in radionuclide therapy and applicable radiobiological investigations.

Induction of high grade astrocytoma (HGA) by protons: molecular mechanisms and RBE considerations.

Protons of a specific energy, 55 MeV, have been found to induce primary high grade astrocytomas (HGA) in the Rhesus monkey (Macaca mulatta). Brain tumors of this type were not induced by protons of other energies (32-2,300 MeV). Induction of HGA has been identified in human patients who have had radiation therapy to the head. We believe that the induction of HGA in the monkey is a consequence of dose distribution, not some unique "toxic" property of protons. Comparison of the human experience with the monkey data indicates the RBE for induction of brain tumors to be about one. It is unlikely that protons cause an unusual change in oncogenic expression, as compared to conventional electromagnetic radiation.