Recent Serendipitous Articles

Patent foramen ovale closure and migraine: science and sensibility.

Expert Rev Neurother. 2010 Sep;10(9):1409-1422

Authors: Gupta VK

Migraine has been associated with patent foramen ovale (PFO), and PFO closure has become the most high-profile nonpharmacologic invasive therapy recommended for the prevention of recurrent migraine attacks, as well as for preventing further attacks in cryptogenic stroke. The results of Migraine Intervention with STARFlex Technology (MIST), a controversial but important recent randomized clinical trial (RCT) of PFO closure for migraine, do not support PFO closure for preventing migraine attacks. All patients with migraine, however, do not have a PFO, and the characteristic periodicity and predictability of migraine cannot be explained on the basis of paradoxical embolism through the PFO. Closure of the PFO or atrial septal defect can aggravate migraine suddenly. PFO increases in size with age, but migraine generally subsides with the passage of years. Serendipity does play a role in some medical discoveries, but in the absence of a logically defensible theoretical basis, chance and statistics can both become misleading. With soft end points, RCTs in migraine patients can generate conflicting and irreconcilable data. RCTs cannot supplant or substitute clinical common sense or justify serendipity. Scientific progress mandates that any serendipitous research must ultimately conform to the principles of the basic sciences surrounding the chance discovery. PFO closure for preventing migraine attacks is an unfortunate, but sobering, chapter in the migraine research saga.

PMID: 20819012 [PubMed - as supplied by publisher]

Serendipity in science: a disappearing element?

Optom Vis Sci. 2010 Sep;87(9):621

Authors: Adams AJ

PMID: 20814263 [PubMed - in process]

The Discovery of Endothelin The Power of Bioassay and the Role of Serendipity In the Discovery of Endothelium-Derived Vasocative Substances.

Pharmacol Res. 2010 Aug 30;

Authors: Rubanyi GM

Significant discoveries in biology and medicine are rare. The progress in these fields is predominantly incremental, but sometimes new observations revolutionize the field by opening new directions in research for decades to come. Two cornerstone observations in the late 1970s and early 1980s are examples of such "revolutionary" events. The first, by Furchgott and Zawadzki, was the discovery of the "obligatory role of the endothelium in vasorelaxation by acetylcholine". The other, by Hickey and colleagues, was the first description and characterization of a vasoconstrictor polypeptide produced by endothelial cells in culture. Both of these observations were achieved by the application of bioassay and serendipity played an important role in each of them. They both represent starting points for rapid growth in research activity world-wide leading to the identification of EDRF as nitric oxide, and the polypeptide EDCF as endothelin a few years later. These early observations also raised interest and initiated intensive R&D activity in the pharma industry culminating in the regulatory approval and marketing of novel medicines treating human diseases. This review describes the events leading to the discovery and early characterization of the peptidergic endothelium-derived constrictor factor, and its purification, sequencing and naming it endothelin.

PMID: 20813186 [PubMed - as supplied by publisher]

Coexisting of aortic arch variation of the left common carotid artery arising from brachiocephalic trunk and absence of the main branches of right subclavian artery: a review of the literature.

Rom J Morphol Embryol. 2010;51(3):569-72

Authors: Karabulut O, Iltimur K, Cudi Tuncer M

The variations in the aortic arch and its branches are of surgical interest. Many anomalies of the aortic arch and great vessels are uncovered as serendipitous findings on imaging studies, in the anatomy laboratory, or at surgery. A 56-year-old woman had an arch angiogram as part of an evaluation for cardiovascular disease. A two-vessel left aortic arch was identified consisting of the brachiocephalic trunk and left subclavian artery. In this study, we present a case of the left common carotid (LCC) artery arising from the brachiocephalic trunk (BT) and absence of the main branches of right subclavian artery in her angiographic imaging findings. There is no previous report about LCC artery arising from BT and absence of the main branches of right subclavian artery in the same person.

PMID: 20809040 [PubMed - in process]

The discovery of the microphthalmia locus and its gene, Mitf.

Pigment Cell Melanoma Res. 2010 Aug 27;

Authors: Arnheiter H

Summary The history of the discovery of the microphthalmia locus and its gene, now called Mitf, is a testament to the triumph of serendipity. Although the first microphthalmia mutation was discovered among the descendants of a mouse that was irradiated for the purpose of mutagenesis, the mutation most likely was not radiation-induced but occurred spontaneously in one of the parents of a later breeding. Although Mitf might eventually have been identified by other molecular genetic techniques, it was first cloned from a chance transgene insertion at the microphthalmia locus. And although Mitf was found to encode a member of a well-known transcription factor family, its analysis might still be in its infancy had Mitf not turned out to be of crucial importance for the physiology and pathology of many distinct organs, including eye, ear, immune system, bone, and skin, and in particular for melanoma. In fact, near seven decades of Mitf research have led to many insights about development, function, degeneration, and malignancies of a number of specific cell types, and it is hoped that these insights will one day lead to therapies benefitting those afflicted with diseases originating in these cell types.

PMID: 20807369 [PubMed - as supplied by publisher]

An alternative point of view: Getting by with less: What's wrong with perfection?

Crit Care Med. 2010 Aug 12;

Authors: Nunnally M

OBJECTIVE:: Predictions about the future impact of technologic and process innovations inspire optimistic visions. Optimism and speculation require a counterweight. Because results often do not turn out as expected, anticipating failure is useful, and anticipating unintended consequences is visionary. MEASUREMENTS:: A history of unfulfilled prognostications was explored with the intent of finding something essential to the complexities of medicine. Do missed predictions signal another side to innovation that also helps us uncover new information about our world? RESULTS:: Serendipity is an important theme in medical innovation. There is no reason to think this will change. Things do not necessarily go as planned, but often the results are as important as the original prediction was supposed to be. It will not be clear where we end up until we get there. CONCLUSIONS:: Ideal goals are useful but speculative and subjective. There in fact might be several ideals and contingency is important. The detours and incidental stops on the way to an ideal are more fruitful than the goal itself.

PMID: 20711064 [PubMed - as supplied by publisher]

Lake-specific variation in growth, migration timing and survival of juvenile sockeye salmon Oncorhynchus nerka: separating environmental from genetic influences.

J Fish Biol. 2010 Aug;77(3):692-705

Authors: Reed TE, Martinek G, Quinn TP

Time series on juvenile life-history traits obtained from sockeye salmon Oncorhynchus nerka were analysed to assess lake-specific environmental influences on juvenile migration timing, size and survival of fish from a common gene pool. Every year for the past two decades, O. nerka have been spawned at a hatchery facility, and the progeny released into two lakes that differ in average summer temperatures, limnological attributes and growth opportunities. Juveniles reared in the warmer, more productive Crosswind Lake were larger and heavier as smolts compared to those from the cooler, less productive Summit Lake and had higher in-lake and subsequent marine survival. Crosswind Lake smolts migrated from the lake to sea slightly earlier in the season but the migration timing distributions overlapped considerably across years. Fry stocking density had a negative effect on smolt length for both lakes, and a negative effect on in-lake survival in Summit Lake. Taken together, the results revealed a strong effect of lake-rearing environment on the expression of life-history variation in O. nerka. The stocking of these lakes each year with juveniles from a single mixed-source population provided a large-scale reverse common-garden experiment, where the same gene pool was exposed to different environments, rather than the different gene pools in the same environment approach typical of evolutionary ecology studies. Other researchers are encouraged to seek and exploit similar serendipitous situations, which might allow environmental and genetic influences on ecologically important traits to be distinguished in natural or semi-natural settings.

PMID: 20701648 [PubMed - in process]

[The ship's log of Ellerbeek: common sense and serendipity in the treatment of scurvy.]

Ned Tijdschr Geneeskd. 2010;154(27):A1881

Authors: van Tellingen C

In accordance with the usual practice, chief surgeon Joan Ellerbeek recorded his observations during his voyage with the East Indiaman Mars to the Cape of Good Hope in 1776 in a logbook for the Dutch East India Company. During the voyage he was confronted with an increasing number of scurvy patients. Intuitive insight and serendipity led him to try using the seaweed ('Gramen Marinum') which had grown on the ship as an anti-scurvy agent, in the empirical and medical tradition of his time. The results were spectacular. Not only James Lind should therefore be credited with the solution of the problem of scurvy. Many before and after him, including Ellerbeek, also made a contribution.

PMID: 20699019 [PubMed - in process]

Curious about Pesticide Action (dagger).

J Agric Food Chem. 2010 Aug 11;

Authors: Casida JE

The safe and effective use of pesticides requires knowledge of their mode of action in pests and adverse effects in nontarget organisms coupled with an understanding of their metabolic activation and detoxification. The author and his laboratory colleagues were privileged to observe, participate in, and sometimes influence these developments for the past six decades. This review considers contributions of the Berkeley and Madison laboratories to understanding insecticides acting at voltage-gated sodium and GABA-gated chloride channels and the nicotinic receptor and at serine hydrolases and other targets as well as the action of insecticide synergists and selected herbicides and fungicides. Some of the discoveries gave new probes, radioligands, photoaffinity labeling reagents, and understanding of reactive intermediates that changed the course of pesticide investigations and related areas of science. The importance of coupling mode of action with metabolism and design with serendipity is illustrated with a wide variety of chemotypes.

PMID: 20698709 [PubMed - as supplied by publisher]

N-Tetrahydrothiochromenoisoxazole-1-carboxamides as selective antagonists of cloned human 5-HT(2B).

Bioorg Med Chem Lett. 2010 Jul 21;

Authors: Kwon YJ, Saubern S, Macdonald JM, Huang XP, Setola V, Roth BL

The serendipitous discovery of N-cyclohexyl-8-fluoro-3,3a,4,9b-tetrahydro-1H-thiochromeno[4,3-c]isoxazole-1-carboxamide as a selective human serotonin 5-HT(2B) antagonist with K(i) of 42+/-5nM is reported herein. A subsequent functional assay indicated little agonist activity compared to 5-HT itself.

PMID: 20692833 [PubMed - as supplied by publisher]