Do we need in-patient units for child and adolescent psychiatry? Data on administrative incidence from 1980-1984 from Vorarlberg/Austria

The question of the necessity of in-patient facilities of the area of (child and) adolescent neuropsychiatry is to be discussed further. The extremely optimistic views on this question of approximately 20 years ago cannot be maintained for the examined area and the examination time. In the LNKH Valduna/Vorarlberg, an establishment that was intended exclusively for adults until 1987, from 1980-1984 (evaluated in detail) and from 1984-1987 a further 60 minors were admitted. The exact evaluation shows that the conspicuousnesses of behaviour of a main group was so clear each time that it could not be treated elsewhere and certainly not in outpatient facilities. In the examined group the amount of patients with behaviour and socialization disorders outweighed by far the psychoses, also a high percentage of patients was multi morbid and/or had multiple handicaps. The resulting conclusion seems to us to be the necessity of setting-up a specific in-patients treatment unit for this group of patients with sufficient infrastructure.     

Development of HPLC plasma assays for CAM 4515 and CAM 4750, two new nonpeptide tachykinin antagonists, and application to bioavailability studies

CAM 4515 and CAM 4750 are new nonpeptide tachykinin NK₁ receptor antagonists with different lipophilicities. Two separate, simple, and sensitive HPLC methods for the quantitation of these two compounds in plasma and the evaluation of their oral bioavailability in rats were developed and validated. Extraction of CAM 4515 from plasma involved protein precipitation with acetonitrile, while that for CAM 4750 involved a one-step liquid-liquid extraction with methylene chloride. The analytes in extracts were chromatographed on a C18 column using two different separation buffers, 47% 0.02 M sodium citrate (pH 3.5)-53% acetonitrile for CAM 4515 and 59% 0.02 M potassium phosphate dibasic (pH 7.0)-41% acetonitrile for CAM 4750, and both compounds were detected by fluorescence (excitation 278 nm; emission 342 nm). Stability profiles of both drugs at −20°C or room temperature in plasma and in reconstituted buffers were good. The limit of quantitation for both drugs was 5 ng ml⁻¹ with good linearity from 5 to 1000 ng ml⁻¹ using 100–200 μl of plasma. Excellent precision (relative standard deviation < 8.3%) and accuracy (relative error ± 9.2%) were observed for both CAM 4515 and CAM 4750. Oral bioavailability studies were conducted for each compound in rats receiving a p.o. dose of 20 mg kg⁻¹ and an i.v. dose of 5 mg kg⁻¹. The absolute oral bioavailability of CAM 4750 (80%) was estimated to be 40-fold greater than that of CAM 4515 (2%). The experimental results suggest that incorporation of a pyridine group into the structural backbone may greatly improve bioavailability.     

Finding a place for needle exchange programs

Using the concepts of stigma, NIMBY and place, this paper examines the difficulties of finding a place for needle exchange programs (NEPs). Data were drawn from semi-structured interviews with NEP staff (Ontario, Canada) that focused on operational policies and routines. An iterative, inductive analytic process was used. NEPs, their staff and clients are not always welcome additions to organizations or communities because of concerns about the ‘dangerousness’ of clients and the potential contamination of communities and workplaces by stigmatized individuals and their artefacts (e.g. contaminated injection equipment). Public parks where a lot of drug ‘action’ takes place are good destinations for outreach workers but these places are contentious sites for NEP activities, particularly when residents do not perceive a need for the program and/or want to redefine their neighbourhoods. Issues of ‘place’ are further complicated when service delivery is mobile. Finding a place within organizations is difficult for NEPs because of concerns about the diversion of limited financial and spatial resources to ‘non-core’ activities and ‘undesirable’ clients. Workers respond to these challenges by contesting the social and spatial boundaries of who is an acceptable client or neighbour and refuting the perceived ‘differentness’ of injection drug users. Implementation of an unpopular service involves a delicate balancing act of interests, understanding of the dynamics of particular communities and a willingness to reinvent and redefine programs. The sociospatial stigmatization of injection drug use has had a negative impact on NEPs, and perhaps limits HIV prevention efforts.     

Exogenous Modulation of TGF-β1 Influences TGF-βR-III-Associated Vascularization during Wound Healing in Irradiated Tissue

BACKGROUND AND PURPOSE: Following preoperative radiotherapy prior to ablative surgery of squamous epithelial cell carcinomas of the head and neck region, wound-healing disorders occur. Previous experimental studies showed altered expression of transforming growth factor-(TGF-)beta isoforms following surgery in irradiated graft beds. Altered levels of TGF-beta(1) are reported to promote fibrosis and to suppress vascularization during wound healing, whereas expression of TGF-beta receptor-III (TGF-betaR-III) is associated with vascularization. The aim of the study was to analyze the influence of anti-TGF-beta(1) treatment on TGF-betaR-III-associated vascularization in the transition area between irradiated graft bed and graft. MATERIAL AND METHODS: Wistar rats (male, weight 300-500 g) underwent preoperative irradiation of the head and neck region with 40 Gy (four fractions of 10 Gy each; n = 16 animals). A free myocutaneous gracilis flap taken from the groin was then transplanted to the neck in all rats. The time interval between operation and transplantation was 4 weeks. Eight animals received 1 micro g anti-TGF-beta(1) into the graft bed by intradermal injection on days 1-7 after surgery. On days 3, 7, 14, 28, 56, and 120, skin samples were taken from the transition area between transplant and graft bed and from the graft bed itself. Immunohistochemistry was performed using the ABC-POX method to analyze the TGF-betaR-III and E-selectin expression. Histomorphometry was performed to analyze the percentage and the area of positively stained vessels. RESULTS: A significantly higher expression of TGF-betaR-III was seen in the irradiated and anti-TGF-beta(1)-treated graft bed in comparison to the group receiving preoperative irradiation followed by transplantation alone. The percentage of TGF-betaR-III positively staining capillaries from the total amount of capillaries in the anti-TGF-beta(1)-treated graft bed was higher than in the group irradiated only. The total area of capillaries was also higher in the TGF-beta(1)-treated group. CONCLUSION: Neutralizing of TGF-beta(1) activity in irradiated tissue undergoing surgery leads to a higher expression of TGF-betaR-III and increased vascularization. TGF-betaR-III seems to be associated with newly formed blood vessels during neovascularization in wound healing.     

Myeloablative 131I-tositumomab radioimmunotherapy in treating non-Hodgkin's lymphoma: comparison of dosimetry based on whole-body retention and dose to critical organ receiving the highest dose.

Myeloablative radioimmunotherapy using (131)I-tositumomab (anti-CD20) monoclonal antibodies is an effective therapy for B-cell non-Hodgkin's lymphoma. The amount of radioactivity for radioimmunotherapy may be determined by several methods, including those based on whole-body retention and on dose to a limiting normal organ. The goal of each approach is to deliver maximal myeloablative amounts of radioactivity within the tolerance of critical normal organs. METHODS: Records of 100 consecutive patients who underwent biodistribution and dosimetry evaluation after tracer infusion of (131)I-tositumomab before radioimmunotherapy were reviewed. We assessed organ and tissue activities over time by serial gamma-camera imaging to calculate radiation-absorbed doses. Organ volumes were determined from CT scans for organ-specific dosimetry. These dose estimates helped us to determine therapy on the basis of projected dose to the critical normal organ receiving a maximum tolerable radiation dose. We compared organ-specific dosimetry for treatment planning with the whole-body dose-assessment method by retrospectively analyzing the differences in projected organ-absorbed doses and their ratios. RESULTS: Mean organ doses per unit of administered activity (mGy/MBq) estimated by both methods were 0.33 for liver and 0.33 for lungs by the whole-body method and 1.52 for liver and 1.74 for lungs by the organ-specific method (P=0.0001). The median differences between methods were 0.92 mGy/MBq (range, 0.36-2.2 mGy/MBq) for lungs, 0.82 mGy/MBq (range, 0.28-1.67 mGy/MBq) for liver, and -0.01 mGy/MBq (range, -0.18-0.16 mGy/MBq) for whole body. The median ratios of the treatment activities based on limiting normal-organ dose were 5.12 (range, 2.33-10.01) for lungs, 4.14 (range, 2.16-6.67) for liver, and 0.94 (range, 0.79-1.22) for whole body. We found substantial differences between the dose estimated by the 2 methods for liver and lungs (P=0.0001). CONCLUSION: Dosimetry based on whole-body retention will underestimate the organ doses, and a preferable approach is to evaluate organ-specific doses by accounting for actual radionuclide biodistribution. Myeloablative treatments based on the latter approach allow administration of the maximum amount of radioactivity while minimizing toxicity.     

Administered radiopharmaceutical doses in children: a survey of 13 pediatric hospitals in North America.

Universally applied standards for administering radiopharmaceutical doses in children do not presently exist. Hence, pediatric radiopharmaceutical dosimetry varies considerably from institution to institution and is generally based on the recommended adult dose adjusted for body mass. METHODS: We surveyed 13 pediatric hospitals in North America to obtain objective data on dosimetry practices for 16 pediatric nuclear medicine examinations, including the minimum total radiopharmaceutical administered dose per examination, the total administered dose based on body mass, and maximum total doses in children. RESULTS: The reported administered doses of radiopharmaceuticals to children vary over a relatively large range, especially with respect to minimum total administered doses. CONCLUSION: This survey has identified a broad range of administered doses directly leading to variability in radiation-absorbed doses to patients. The nuclear medicine community should develop pediatric standards for radiopharmaceutical administered doses and reduce radiation exposure in children, such as through the use of modern software reconstruction techniques.     

Adequacy of the epinephrine autoinjector needle length in delivering epinephrine to the intramuscular tissues.

BACKGROUND: Epinephrine injected by an autoinjector in the anterolateral aspect of the thigh is the standard of care in the emergency self-treatment of anaphylaxis. In the United States, the autoinjector EpiPen is widely used for the self-treatment of anaphylaxis. OBJECTIVE: To investigate whether EpiPen autoinjector, with a needle length of 1.43 cm, is sufficient for intramuscular delivery of epinephrine in men and women. METHODS: The distance from skin to muscle in the anterolateral aspect of the thigh was measured in 50 men and 50 women who had undergone computed tomography of the thighs for other medical reasons. For each individual, body mass index (BMI; a measure of weight in kilograms divided by the square of height in meters) was also calculated, and the individuals were classified as underweight (BMI, < 18.5), normal (BMI, 18.5-24.9), overweight (BMI, 25.0-29.9), and obese (BMI, > or = 30.0) using standard definition. RESULTS: In the study participants the mean +/- SD distance from skin to muscle was 0.66 +/- 0.47 cm for men and 1.48 +/- 0.72 cm for women (P < .001). One man (obese at a BMI of 42.2) and 21 women (11 obese with a mean BMI of 35.2, 6 overweight with a mean BMI of 30.1, and 4 normal with a mean BMI of 24.5) had a greater distance from skin to muscle than the EpiPen needle length of 1.43 cm. CONCLUSION: The distance from skin to muscle for the anterolateral aspect of the thigh is higher in women compared with men. This difference suggests that EpiPen may not deliver epinephrine to the intramuscular tissue in many women.