Laboratory tests commonly used in complementary and alternative medicine: a review of the evidence.

It is increasingly easy for the general public to access a wide range of laboratory tests. Tests can be ordered online with little or no input from a health professional. The complementary and alternative medicine (CAM) community promote and sell a wide range of tests, many of which are of dubious clinical significance. Many have little or no clinical utility and have been widely discredited, whilst others are established tests that are used for unvalidated purposes. They range from the highly complex, employing state of the art technology, e.g. heavy metal analysis using inductively coupled plasma-mass spectrometry, to the rudimentary, e.g. live blood cell analysis. Results of 'CAM tests' are often accompanied by extensive clinical interpretations which may recommend, or be used to justify, unnecessary or harmful treatments. There are now a small number of laboratories across the globe that specialize in CAM testing. Some CAM laboratories operate completely outside of any accreditation programme whilst others are fully accredited to the standard of established clinical laboratories. In this review, we explore CAM testing in the United States, the United Kingdom and Australia with a focus on the common tests on offer, how they are reported, the evidence base for their clinical application and the regulations governing their use. We will also review proposed changed to in-vitro diagnostic device regulations and how these might impact on CAM testing.

Cyclical Cushing's: how best to catch the ups and downs.

A 68-year-old man with a background of hypertension and type 2 diabetes presented with fluctuating symptoms of muscle aches and pains and tiredness. His initial work-up for the possibility of hypercortisolaemia showed a completely variable pattern, with 24-hour cortisol excretion and serum cortisol post 1 mg dexamethasone suppression test ranging from normal to significantly elevated. A series of salivary cortisol with symptom diary confirmed the cyclical nature of hypercortisolaemia, and his concomitant adrenocorticotropic hormone (ACTH) levels were elevated. An inferior petrosal sinus sampling, performed during hypercortisolaemic phase of his cycle,suggested a central source of ACTH secretion. He had unsuccessful exploration of his pituitary and was eventually treated with bilateral adrenalectomy followed by lifelong steroid replacement. His symptoms improved immediately, and he came off his oral hypoglycaemic and antihypertensive agents within 6 months following his surgery.

Phenindione interference in enzymatic creatinine assay - A case report.

Enzymatic creatinine assays are considered superior to Jaffe assays due to greater analytical specificity. We report a case of phenindione interference with an enzymatic assay resulting in significant misclassification in a patient with chronic kidney disease (CKD). Analysis of creatinine values of a further 36 patients who were treated with phenindione showed significant negative interference of phenindione with the Roche enzymatic creatinine assay.

Folding kinetics of the human prion protein probed by temperature jump.

Temperature-jump perturbation was used to examine the relaxation kinetics of folding of the human prion protein. Measured rates were very fast (approximately 3,000 s(-1)), with the extrapolated folding rate constant at approximately 20 degrees C in physiological conditions reaching 20,000 s(-1). By a mutational analysis of core residues, we found that only 2, on the interface of helices 2 and 3, have significant phi-values in the transition state. Interestingly, a mutation sandwiched between the above 2 residues on the helix-helix contact interface had very little effect on the overall free energy of folding but led to the formation of a monomeric misfolded state, which had to unfold to acquire the native PrP(C) conformation. Another mutation that led to a marked destabilization of the native fold also formed a misfolded intermediate, but this was aggregation-prone despite the native state of this mutant being soluble. Taken together, the data imply that this fast-folding protein has a transition state that is not compact (m value analysis gives a beta(t) value of only 0.3) but contains a developing nucleus between helices 2 and 3. The fact that a mutation in this nucleus had a negligible effect on stability but still led to formation of aberrant conformations during folding implies an easily perturbed folding mechanism. It is notable that in inherited forms of human prion disease, where point mutations produce a lethal dominant condition, 20 of the 33 amino acid replacements occur in the helix-2/3 sequence.