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.     

The combination of prazosin and verapamil in the treatment of essential hypertension

An exaggerated fall in blood pressure has been reported with the combination of an alpha 1-blocker and a calcium antagonist. This study investigated, in a placebo-controlled, randomized crossover trial, the clinical usefulness of the combination of prazosin (2 mg b.i.d.) and verapamil (160 mg b.i.d.). Therapeutic efficacy was monitored at regular outpatient visits: average supine and erect blood pressures were, respectively, 175/99 and 176/103 mm Hg with placebo, 160/91 and 164/96 mm Hg with single drug treatment, and 152/84 and 152/89 mm Hg with combination therapy. This significant and clinically useful reduction in blood pressure had an overall magnitude of approximately 28/18 mm Hg (supine) and 29/19 mm Hg (erect). Further measurements were made during a series of intensive study days, and the most important additional finding was a pharmacokinetic interaction that resulted in increased peak concentrations and bioavailability of prazosin. In conclusion, the combination of prazosin and verapamil proved effective in the treatment of 12 patients with essential hypertension who had been poorly responsive to conventional treatment with a beta-blocker and thiazide diuretic.     

Effects of sensory and motor functioning on adult intellectual performance

This study examined longitudinal health and intelligence data to determine whether sensory or motor deficits account for some of the age-related intellectual changes that are commonly seen from midlife onward. Although sensory and motor functioning did not account for the age-related decrements in performance on speeded, visual perceptual tasks found for this sample in previous work, we did find that hearing deficits added error variance to performance estimates on two verbal subtests of the Wechsler scales.     

Clinical risk management in anaesthesia

Contin Educ Anaesth Crit     

Linear and angular measurements of computer-generated models: are they accurate, valid, and reliable?

INTRODUCTION: Traditional advanced imaging modalities such as CT and MRI are limited in their ability to perform accurate linear distance and angular measurements regardless of anatomical orientation. The construction of 3D models has been used to perform anthropometric analyses as well as in the reconstruction of rapid prototypes. We hypothesized that such measurements would be precise to within 2 mm or 2 degrees of measurements performed with a coordinate measurement machine (CMM). We also hypothesized that there would be a high degree of interobserver reliability with these measurements. MATERIALS AND METHODS: Multiple aluminum screws were implanted in various positions in three foam pelvises which were subsequently scanned by CT and rendered as 3D models using a commercially available software package (Mimics). Linear and angular measurements were performed using a CMM machine, the software package, and a dial caliper or goniometer. The deviation of the measurements from the CMM data was compared using ANOVA. The interobserver reliability of both the manual and computer-generated measurements was calculated. RESULTS: The mean difference between the CMM distances and those measured manually and with the software was 2.12 +/- 1.20 mm and 1.57 +/- 1.05 mm, respectively. The mean difference between the CMM angular measurements and the angular measurements performed manually and with the software was 4.07 +/- 4.70 degrees and 1.62 +/- 1.32 degrees, respectively. In all cases, the manual measurements were significantly less accurate (p < 0.0001) and there was a high degree of interobserver reliability. CONCLUSIONS: Computer-generated measurements taken from three-dimensionally reconstructed models are more accurate than manual measurements and are within 2 mm and 2 degrees of measurements performed with a CMM. These measurements have high interobserver reliability.     

Cardiovascular intervention for high-risk families: the Heart Smart Program

The Heart Smart Family Health Promotion Program is a multidisciplinary, school-based program for cardiovascular risk reduction among high-risk children and their families. As a program that includes young adults at high risk, it is adaptable to a clinical practice. Nineteen fourth and fifth graders were selected as probands for elevated risk factors after a general screening to identify families for an intervention program. Twenty-three parents participated in a 12-week program focused on eating, exercise, and smoking behavior changes enhanced by behavicral support strategies. Weekly sessions were held in the auditorium/cafeteria of the elementary school and consisted of orientation and presentations, cardiovascular (CV) screening with medical feedback, activities, self-monitoring, counseling, and contingency contracting. Information gathered before and after the program included medical history, CV health knowledge and relevant behavior, blood pressure, serum lipid and lipoprotein values, anthropometric measurements, and urine electrolyte excretion. Both children and parents showed positive changes in eating habits and physical activity and significant changes in knowledge and blood pressure levels, while the children halted their weight gain. We believe this multidisciplinary, behavior-oriented, school-based program can be an effective cardiovascular risk intervention adaptable for a clinical office practice.     

FACTORS AFFECTING THE SELECTION OF PRIMARY MEDICAL CARE AGENCY IN THE WESTERN REGION OF MELBOURNE: AN INTERVIEW STUDY OF ADULT PATIENTS

An interview study investigating attitudinal and other factors influencing the selection of primary medical care (PMC) agency is described. It focuses on adult patients excluding those with trauma of medical/surgical emergencies and was conducted in part of the Western Region of Melbourne in late 1983, the period immediately prior to the introduction of Medicare. It is based on a cross-sectional survey of in-hours attenders of eight general practices (GP), the Western Region (Community) Health Centre (WRCHC) and the general clinic of the casualty department at the Western General Hospital (WGH). Attenders of these different services differed significantly in their socio-demographic characteristics. WGH attenders were significantly younger and had migrated from non-English speaking countries significantly more often. Male attenders at the WGH had significantly lower socioeconomic status. 71 per cent being not in the workforce. The most commonly stated reasons for attendance at particular services generally were “closeness to home, work”, “recommendation” and “good service”. Reasons given by attenders at the different clinics generally were similar. However GP attenders offered “good service” significantly more often as a reason for choice; WGH attenders offered “cheap/economic reasons” significantly more often and “recommendation” significantly less so. WRCHC attenders offered “workers' compensation” significantly more often. Thirty per cent of attenders overall had attended other than their current clinic during their past three to four illness episodes. While a large majority of patients still attend GP for PMC it is concluded that a pluralist model recognising the legitimacy of different PMC arrangements and multiple use of them by individuals best meets community need. This is likely to be even more true under Medicare. It is concluded that instrumental factors and social networks are important in the selection of PMC, particularly given the limited knowledge of respondents about health services. It is also concluded that cost and economic factors have been given undue weight in selection of primary medical care agency. The use of the WGH casualty department by groups not in the work force, given no real financial advantage in doing so, requires further study.