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.     

Recombinant forms of Gerbich blood group antigens: expression and purification.

Recombinant forms of normal glycophorin C (GPC), carrying the high frequency Gerbich blood group antigens, and its natural deletion mutants of Yus and Ge type (all combined with oligohistidyl tag) were expressed in CHO and COS 7 cells. The stable expression of all recombinant forms of GPC in CHO cells was obtained, but the level of expression was low and detectable only by flow cytometry. The high level of transient expression of GPC recombinant forms in COS 7 cells allowed their purification on Ni-NTA-agarose. The purified recombinant GPC and mutants of Yus and Ge type behaved in SDS-PAGE similarly to normal GPC forms from RBC membranes. The recombinant GPC.Yus and GPC.Ge mutants appeared as diffuse bands, suggesting the similar heterogeneity of glycosylation that was observed in natural GPC.Yus and GPC.Ge glycoproteins. The flow cytometry analysis of the transfected CHO and COS 7 cells showed that binding of anti-GPC monoclonal antibodies to GPC variants was accordant with the known fine specificity of these antibodies. The obtained recombinant forms of GPC carrying common Gerbich antigens may be useful in serology, and also as model molecules for structure-function studies.     

MEASUREMENTS OF INTERFACE PRESSURE BETWEEN BODY SITES AND THE SURFACES OF FOUR SPECIALISED AIR MATTRESSES

SUMMARY Four specialised air mattresses had interface pressure measured under six body sites prone to pressure sores in 10 subjects, supine and sitting. The mattresses were the Clinirest (SSI) and FirstStep (KCI) continuous airflow mattress overlays, and Airwave (Pegasus) and Nimbus (Huntleigh) alternating pressure air mattresses. On the mattress overlays, average supine interface pressures were 2.33 kPa (scapula), 4.15 kPa (elbow), 1.94 kPa (sacrum) and 2.79 kPa (buttock), although they were higher at the occiput (7.97 kPa) and heel (11.7 kPa). The alternating pressure air mattresses had an average minimum interface pressure close to zero for three sites, rising to 4.28 kPa under the heel. Average maximum interface pressures were 8.61 kPa (occiput), 5.21 kPa (scapula), 4.90 (elbow), 4.85 kPa (sacrum), 4.61 kPa (buttock) and 13.2 kPa (heel). No accepted scientific method exists for comparing the two types of mattress. Our data suggest a clinical benefit at the occiput and heel (supine) in using an alternating pressure air mattress and a benefit in using a continuous airflow mattress overlay at other sites.     

Ninety-Six Five-Year Survivors After Liver Resection for Metastatic Colorectal Cancer

Background: Studies have consistently confirmed the benefit of liver resection for metastatic colorectal cancer. Few reports, however, have a long enough followup or sufficient 5-year survivors to study the clinical course of patients beyond 5 years.

Study Design: From July 1985 through December 1991, 456 patients underwent liver resection for colorectal metastases. Ninety-six actual 5-year survivors (21%) were identified and their clinical course retrospectively reviewed.

Results: Five-year survivors (n = 96) were more likely to have a Duke’s B primary colorectal carcinoma, fewer than four metastatic lesions, unilobar disease, and a negative histologic margin when compared with patients not surviving 5 years (n = 298). Forty-four (46%) of the 96 five-year survivors had a recurrence after hepatectomy. Of these 44, 19 (43%) were rendered disease free after further treatment. Overall, 71 of the 96 five-year survivors were free of disease at last followup. The actuarial 10-year survival of this group was 78%.

Conclusions: Patients that are disease free 5 years after liver resection are likely to have been cured by liver resection. Patients should be aggressively followed for recurrence because of the potential for further treatment and longterm survival.     

Treatment of ABO Hemolytic Disease with Synthetic Blood Group Trisaccharides

Thirteen infants, 10 with A-O and 3 with B-O hemolytic disease of the newborn (ABO-HDN), were treated with synthetic A or B blood group trisaccharides (ATS, BTS) which cause dissociation of maternal antibody bound to infant red cells. The clinical outcome was compared with that of a control group of 21 infants treated with phototherapy during the preceding year. Exchange transfusion was required in 2 out of 13 infants in the experimental group and in 7 in the control group. A randomized prospective controlled study is necessary to confirm these results.     

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.