In this, the autumn of her career, Piscator finds herself composing her last column. She reflects on the massive change in landscape of laboratory medicine and in particular the most recent changes in scientific and medical publishing since she took over the column some 12 y ago. It was with some trepidation that she stepped into the formidable shoes of the first, ground-breaking incarnation of Piscator. In this age of multimedia, it is hard to credit that her original hunting ground for copy was the dusty confines of the Medical School library with its deathly quiet and shelves upon shelves of archived paper journals and weighty tomes. Fast-forward a decade and the library is unrecognizable for its multitude of screens and terminals with paper – print very much taking second place. A decorative panel at the entrance to this new learning environment etched with a quote of John F Kennedy exhorts us all to embrace change: ‘Change is the law of life. And those who look only to the past or present are certain to miss the future’.

The way we access information has changed forever. An excellent example is the online video accompanying a case report of a patient who developed hypocalcaemia after thyroid surgery (NEJM 2012;367:e15). The video illustrates Chovstek's and Trousseau's sign when his calcium fell to 1.45 mmol/L. While Chovstek's sign is neither sensitive nor specific for hypocalcaemia, Trousseau's sign is present in up to 94% of patients with hypocalcaemia. In contrast to this iatrogenic cause of hypoparathyroidism, surgical removal of the glands is now the accepted treatment modality for hyperparathyroidism even when the patient is asymptomatic. A recent review (BMJ 2012;367:e1013) of primary hyperparathyroidism discusses how the majority of patients come to medical attention – it is no longer with the clinical triad of ‘stones, bones and groans’. Rather they are identified through routine biochemical screening. Nor is surgery the only option – medical management with calcium-lowering agents is available for those who are not candidates for surgery. And this is an example of how the diagnosis and treatment has changed radically during the course of Piscator's working life, in no small part due to the efforts of former colleagues who developed rapid, specific and sensitive immunoassays for parathyroid hormone.

Though sometimes she feels it is more ‘Plus ça change plus c'est la même chose’ as the same hoary, old chestnuts appear in the literature with indecent frequency. Witness the review of the value of ‘spot’, i.e. random urine collections in the diagnosis of pre-eclampsia. (BMJ 2012;345:e4342). Specifically the article evaluated through meta-analysis of published studies, the value of random urinary protein and albumin-to-creatinine ratios for detection of significant proteinuria or adverse pregnancy outcome in women with suspected pre-eclampsia. The conclusion was that while the estimate of protein-to-creatinine ratio showed promising diagnostic value in suspected pre-eclampsia, there was no such evidence for the use of albumin-to-creatinine ratio. Similarly the diagnostic value of amylase and lipase has come under recent scrutiny (BMJ Open 2012;2:e001471). This online article posed the question: is serum amylase still required to diagnose acute pancreatitis? The authors refer to the current British Society of Gastroenterology guidelines for the management of acute pancreatitis. These propose that clinical presentation with increased plasma activities of pancreatic enzymes, preferably lipase, is the cornerstone of diagnosis. Various studies have demonstrated that serum lipase has better sensitivity and specificity compared with serum amylase in diagnosing pancreatitis. In a retrospective study of 151 patients, the authors demonstrated that the sensitivity and specificity of serum lipase was superior to amylase and that a single lipase assay in all patients presenting with abdominal pain to the surgical admission unit would result in a potential saving of £900 a year. Not a huge saving one may contest. Moreover, there was no mention of any laboratory input to either of these studies.

One change in content to be applauded is the inclusion of the patient experience – particularly when the patient is a writer with several bestsellers to his name. A particularly poignant but ultimately positive personal experience was described when the author fell foul of poisonous fungi (BMJ 2012;345:e5262). He describes foraging in a Scottish woodland a couple of years ago with his family and mistakenly collecting Cortinarius speciossimus, thinking they were either ceps or chanterelles. Within days he was on the renal unit of the local hospital looking at years of dialysis as this genus of fungus is a cousin of the deadly webcap and causes irreversible acute kidney failure. Eventually and reluctantly he accepted the offer of a transplant from his daughter. In perhaps the only way an author could, he described how immediately post-transplant his new kidney was ‘working like a Ferrari’.

And if Piscator is to be allowed some indulgence in this her swansong column, it is being able to draw attention to cystic fibrosis (CF). As the medical and scientific advances of the last century roll out to the emerging economies around the world, she for one was ignorant of the fact that neonatal screening for the condition was implemented in some states in Brazil ahead of the UK. An interesting annotation on a presenting feature of this condition which is now rarely seen in the developed, northern climates concerns hyponatraemia (J Pediatr 2012;161:285–9). Among a cohort of 20 infants identified through neonatal screening, 95% of them had hyponatraemia at first medical contact and a further 10% had severe hyponatraemia with sodium less than 120 mol/L. The authors caution that in tropical climates, hyponatraemia is one of the first manifestations of the disease.

But perhaps the best feel-good story in relation to this condition is the news that a viable treatment is on the horizon. While trials of gene therapy to ameliorate the lung condition have commenced in the UK, our American cousins have embarked on a different therapeutic strategy (NEJM 2011;365:1663–72). Hundreds of thousands of chemical compounds were screened for their ability to restore the defective chloride channel function. One of these named IVACAFTOR was shown to increase the length of time the activated chloride channel could remain open to transmit chloride ions. In a study, 161 patients with at least 1 specific mutation (G551D) in the cystic fibrosis transmembrane conductance regulator gene were recruited for clinical evaluation of the drug potency. The patients demonstrated an increase of 10% in markers of pulmonary function. However, the most impressive finding was the average decrease in sweat chloride concentration of 48 mmol/L rendering most determinations of this parameter within the normal range. This confirms the systemic effect of the drug and, for the first time in the 23 y since the identification of the CF gene and its mutations, a viable treatment is within reach.

Finally Piscator could not finish without a whimsical twist in the tail. The gene responsible for the distinctive fur markings of the feline species – from domestic tabbies to cheetahs – has been identified (Science 2012:1536–41). The gene is a transmembrane aminopeptidase and encodes a membrane-bound metalloprotease. So in the future with a bit of transformative pharmacotherapy, as described above, the leopard may conceivably be able to change its spots.

Editor-in-Chief's note: Piscator has signed-off in style. We would like to thank her for the excellent articles she has penned for the Annals over the years and the enjoyment she has brought our readers.