166Ho-DOTMP radiation-absorbed dose estimation for skeletal targeted radiotherapy.

166Ho-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylene-phosphonate (DOTMP) is a tetraphosphonate molecule radiolabeled with 166Ho that localizes to bone surfaces. This study evaluated pharmacokinetics and radiation-absorbed dose to all organs from this beta-emitting radiopharmaceutical. METHODS: After two 1.1-GBq administrations of 166Ho-DOTMP, data from whole-body counting using a gamma-camera or uptake probe were assessed for reproducibility of whole-body retention in 12 patients with multiple myeloma. The radiation-absorbed dose to normal organs was estimated using MIRD methodology, applying residence times and S values for 166Ho. Marrow dose was estimated from measured activity retained after 18 h. The activity to deliver a therapeutic dose of 25 Gy to the marrow was determined. Methods based on region-of-interest (ROI) and whole-body clearance were evaluated to estimate kidney activity, because the radiotracer is rapidly excreted in the urine. The dose to the surface of the bladder wall was estimated using a dynamic bladder model. RESULTS: In clinical practice, gamma-camera methods were more reliable than uptake probe-based methods for whole-body counting. The intrapatient variability of dose calculations was less than 10% between the 2 tracer studies. Skeletal uptake of 166Ho-DOTMP varied from 19% to 39% (mean, 28%). The activity of 166Ho prescribed for therapy ranged from 38 to 67 GBq (1,030-1,810 mCi). After high-dose therapy, the estimates of absorbed dose to the kidney varied from 1.6 to 4 Gy using the whole-body clearance-based method and from 8.3 to 17.3 Gy using the ROI-based method. Bladder dose ranged from 10 to 20 Gy, bone surface dose ranged from 39 to 57 Gy, and doses to other organs were less than 2 Gy for all patients. Repetitive administration had no impact on tracer biodistribution, pharmacokinetics, or organ dose. CONCLUSION: Pharmacokinetics analysis validated gamma-camera whole-body counting of 166Ho as an appropriate approach to assess clearance and to estimate radiation-absorbed dose to normal organs except the kidneys. Quantitative gamma-camera imaging is difficult and requires scatter subtraction because of the multiple energy emissions of 166Ho. Kidney dose estimates were approximately 5-fold higher when the ROI-based method was used rather than the clearance-based model, and neither appeared reliable. In future clinical trials with 166Ho-DOTMP, we recommend that dose estimation based on the methods described here be used for all organs except the kidneys. Assumptions for the kidney dose require further evaluation.     

Additive Effects of Sevoflurane and Propofol on γ-Aminobutyric Acid Receptor Function

Background: Previous studies have shown that propofol and sevoflurane enhance the function of [gamma]-aminobutyric acid type A (GABAA) receptors. However, it is not known whether these two drugs modulate the same molecular pathways. In addition, little is known about receptor function in the presence of both propofol and sevoflurane. The aim of this study was to better understand the interactions of propofol and sevoflurane with the GABAA receptor.

Methods: Wild-type [alpha]1, [beta]2, [gamma]2s GABAA receptor subunit complementary DNAs were transfected into human embryonic kidney cells grown on glass coverslips using a calcium phosphate transfection method. After transfection (36-72 h), cells were whole cell patch clamped and exposed to combinations of the following: 0.3-1,000 [mu]m [gamma]-aminobutyric acid (GABA), 0-10 [mu]m propofol, and 0-1,650 [mu]m sevoflurane. Chemicals were delivered to the cells using two 10-channel infusion pumps and a rapid solution exchanger.

Results: Both propofol and sevoflurane alone enhanced the amplitude of GABAA receptor responses to submaximal concentrations of GABA in a dose-dependent manner. The enhancement was underpinned by an increase in the apparent affinity of the receptor for GABA. Coapplication of both anesthetics further enhanced the apparent affinity of the receptor for GABA.     

Posttraumatic stress disorder and associated risk factors in Canadian peacekeeping veterans with health-related disabilities.

OBJECTIVES: This study investigates posttraumatic stress disorder (PTSD) and its associated risk factors in a random, national, Canadian sample of United Nations peacekeeping veterans with service-related disabilities. METHODS: Participants included 1016 male veterans (age < 65 years) who served in the Canadian Forces from 1990 to 1999 and were selected from a larger random sample of 1968 veterans who voluntarily and anonymously completed a general health survey conducted by Veterans Affairs Canada in 1999. Survey instruments included the PTSD Checklist-Military Version (PCL-M), Center for Epidemiological Studies-Depression Scale (CES-D), and questionnaires regarding life events during the past year, current stressors, sociodemographic characteristics, and military history. RESULTS: We found that rates of probable PTSD (PCL-M score > 50) among veterans were 10.92% for veterans deployed once and 14.84% for those deployed more than once. The rates of probable clinical depression (CES-D score > 16) were 30.35% for veterans deployed once and 32.62% for those deployed more than once. We found that, in multivariate analyses, probable PTSD rates and PTSD severity were associated with younger age, single marital status, and deployment frequency. CONCLUSIONS: PTSD is an important health concern in the veteran population. Understanding such risk factors as younger age and unmarried status can help predict morbidity among trauma-exposed veterans.     

A novel hybridoma antibody (PASE/4LJ) to human prostatic acid phosphatase suitable for immunohistochemistry

A murine monoclonal antibody PASE/4LJ to prostatic acid phosphatase (PAP) was used to immunostain a wide variety of sections of benign and malignant tissues (654 blocks). Non-neoplastic adult and fetal prostatic glands, primary and metastatic prostatic carcinomas, and scattered cells in prostatic and penile urethra were positive. Rat, dog and rabbit prostates were negative. Nine of 400 tumours of non-prostatic origin showed some positivity: 6/36 carcinoids, 1/9 islet cell tumours, 1/55 ovarian adenocarcinomas (serous) and one carcinosarcoma of the lung (epithelial portion). Positive staining was seen in islet cells in 4/5 specimens of normal pancreas, and in 4/9 blocks of normal pancreas surrounding a pancreatic tumour. Loops of Henle, maculae densae, and distal tubules in 10/10 fetal and 2/9 adult kidneys were also positive, with proximal tubules and collecting ducts negative. All other 159 blocks of non-neoplastic adult and fetal tissues were negative. The antibody was also affinity purified from ascitic fluid, and shown not to inhibit the enzyme activity of prostatic acid phosphatase.     

Occupational therapy workforce needs: a model for demand-based studies.

PURPOSE: To provide a model for assessing occupational therapy workforce needs by using a demand-based approach to determine current workforce status in the Northwest region. Regional information may have implications for addressing national occupational therapy service needs. METHOD: A questionnaire was sent to a proportional random sample of 234 facilities that hire occupational therapy practitioners. Data were collected in July-August 2003 using structured mailing and follow-up procedures. RESULTS: Response rate was 79%. Twenty-four percent reported occupational therapy vacancies and 11% occupational therapy assistant vacancies; 48% predicted an increase in occupational therapy positions in the next 2 years and 41% an increase in occupational therapy assistant positions. Sixty-three percent of respondents reported difficulty in hiring. DISCUSSION: This study identifies an occupational therapy workforce shortage in the Northwest. Management of a shortage is critical, for even short-term adjustments could lead to permanent changes in service provision. This study demonstrates the importance of current information on the status of the national workforce and serves as a model for future studies.     

Resting and total energy expenditure in patients with ischemic heart disease.

Total energy expenditure (TEE) was measured by doubly labeled water in 13 preoperative patients undergoing elective coronary artery surgery and compared to resting energy expenditure (REE) measured by indirect calorimetry (IC) calculated from the Harris-Benedict (HB) formula or from formulas based on midarm circumference and arm muscle circumference. Mean REE measured by IC and calculated from the HB, midarm circumference, arm muscle circumference formulas were 62, 75, 62, and 69%, respectively, of TEE measured by doubly labeled water. REE measured by IC correlated significantly with that predicted by the HB (p = 0.006) but not the anthropometric formulas. The relationship between REE derived from anthropometric predictive formulas and REE measured by IC is altered in ischemic heart disease.     

Preoperation interviews: a nursing intervention to reduce patients' anxiety.

A quasi-experimental study was conducted to evaluate the effect of preoperative interviews on patients' anxiety levels. A convenience sample of 60 was assigned between two groups of equal size: a treatment group in which subjects were interviewed by a perioperative nurse or a control group in which subjects were not interviewed. All subjects completed state-trait Anxiety Inventory questionnaires. Group comparison using analysis of covariance showed subjects who were interviewed by the perioperative nurse reported significantly less anxiety than control group subjects.     

世界脊髓损伤研究的代表性方向

我们现在要尽量使这些治疗方法进入临床试验证明他们的可行性现在脊髓损伤的临床试验基金很有限，所以只有很少的这些治疗方法真正用于病人主要的制药厂开始对脊髓损伤治疗产生兴趣，我们现在还有很多工作要做，但是前景方向十分清楚，我们需要努力快速的工作。