Minimum distinguishable difference in concentration: a clinically oriented translation of assay precision summaries.

A trend to market-driven health care in many parts of the world is focusing increasing attention on getting maximum value from available resources. Laboratories are not exempted. Well-informed clinical input has a potentially valuable role in any laboratory rationalization process. However, a communication difficulty exists in the sense that, although laboratory workers, commercial developers, regulatory bodies, etc., are thoroughly conditioned to using assay coefficient of variation as a general performance measure (for excellent reasons), this is not necessarily the most intuitive or informative scale from a clinician's perspective. Here we use routine clinical data from an immunoradiometric assay of thyrotropin to illustrate, first, a general approach to estimation and prediction of reproducibility, and second, an alternative summary that expresses the discriminatory power of an assay. This latter measure, our experience suggests, is more suited to the way clinicians perceive assays and assay results. The overall aim is improved clinician/laboratory communication.     

Effect of low dietary calcium on bone metabolism in the SENCAR mouse

The SENCAR (sensitive to carcinogenesis) mouse is a unique tool for investigating the interaction between a specific defect in intracellular signaling, dietary calcium, and metabolic bone disease. The SENCAR mouse was developed by selective breeding for enhanced sensitivity to two-stage carcinogenesis. Its major genetic defect, which renders it exquisitely sensitive to stimulation with diacylglycerol or phorbol esters, is in the regulatory domain of protein kinase C, one of the primary intracellular mediators of hormonal effects. At sexual maturity, SENCAR mice are large and have big bones, but our previous pharmacokinetic studies showed that they accumulate lesscalcium under normal conditions and lose more calcium under adverse conditions than do other, standard strains of mice. To histologically define the effect of low dietary calcium on bone metabolism, we performed histomorphometric analysis of tetracycline-labeled sections of femoral bone from male SENCAR mice maintained on calcium-sufficient and calcium-deficient diets during the critical period from 10 to 14 weeks of age. The bone volume, absolute osteoid volume, and mineral apposition rate were lower at 14 than at 10 weeks of age in SENCAR mice fed 0.02 or 0.6% calcium diets. Calcium deficiency increased the architectural disarray and the probability of observing focal discontinuities in the growth plate. Thus, characteristic features of impaired bone metabolism (low bone volume and apposition rate) develop early in SENCAR mice and are exacerbated by low dietary calcium. Detailed examinations of the histology and biochemistry of SENCAR mouse bone will provide insights into the mechanisms by which specific defects in the signal transduction of protein kinase C contribute to impaired bone metabolism.     

Academic,community and state mental health program collaboration: The Oregon experience

The authors review the relationship that has evolved over the years between the Department of Psychiatry at Oregon Health Sciences University and Oregon's community and state mental health programs. They describe the compatibility that exists between the basic requirements of academic psychiatry departments and public mental health programs and demonstrate how these organizations have been able to fulfill one another's needs in Oregon. Specific examples of successful collaborations in the areas of education, administration, research, and service are presented to illustrate how relationships that have been designed to meet specific requirements of one organization can fulfill many requirements of both. Suggestions are provided for those organizations contemplating similar collaborative endeavors.     

Epidemic dysentery caused by Shigella dysenteriae type 1: a sentinel site surveillance of antimicrobial resistance patterns in Burundi.

Annual epidemics of bacillary dysentery have been a public health problem in Burundi for the last 14 years. Recent civil unrest, resulting in the displacement of large numbers of people into refugee settlements, has aggravated the situation. We report the results of a nationwide, health-centre based, sentinel site survey to check the drug resistance of Shigella dysenteriae type 1 (Sd1), the causal organism of such epidemics. Shigella spp. (of which 97% were Sd1) were isolated from 73% of the 126 specimens collected from six main sites around the country. There was no difference in culture results from fresh and frozen stool specimens. Overall Sd1 resistance to commonly available antibiotics (sulfamethoxazole + trimethoprim, ampicillin, tetracycline, and chloramphenicol) varied from 77% to 99% and was fairly uniformly distributed over the country. All Sd1 isolates were susceptible to newer drugs, such as ciprofloxacin and ceftriaxone. Resistance to nalidixic acid, the current first line of treatment for bacillary dysentery in Burundi, varied from 8% to 83% in the different sentinel sites; global resistance was 57%.     

Concurrent ferromagnetic hyperthermia and 125I brachytherapy in a rabbit choroidal melanoma model.

Ferromagnetic (FM) thermoseeds and radioactive (125I) seeds were combined in an episcleral plaque to give concurrent hyperthermia and irradiation for enhanced tumour destruction. A Greene melanoma cell line was utilized to study the interaction between these treatment modalities. We attached five FM thermoseeds (with an operating temperature of 48 degrees C) in parallel with alternating rows of 125I seeds onto the inner surface of each 14 mm Silastic plaque. Plaques were centred over a 3-6 mm (diameter) intraocular melanoma in each rabbit. Some rabbits were then placed within a heating coil, and their eye tumours were warmed rapidly to therapeutic temperatures (43.6 degrees C across the tumour base) while the temperature of normal conjunctiva across the globe did not exceed 38.5 degrees C. Analysis of 49 treated eye melanomas showed 50% local tumour control at 41.7 Gy for 125I alone, whereas only 9.5 Gy were needed to give the same local control rate after 125I with concurrent FM hyperthermia. Thus, a thermal enhancement ratio of 4.4 was obtained. Hyperthermia alone gave a 20% tumour response rate, but responses were only temporary. We conclude that FM thermoseeds can be used to deliver biologically effective hyperthermia concurrently with radiation, thereby reducing the dose of radiation needed for tumour control.