Cryptochrome mediated magnetic sensitivity in Arabidopsis occurs independently of light-induced electron transfer to the flavin.

Cryptochromes are highly conserved blue light-absorbing flavoproteins which function as photoreceptors during plant development and in the entrainment of the circadian clock in animals. They have been linked to perception of electromagnetic fields in many organisms including plants, flies, and humans. The mechanism of magnetic field perception by cryptochromes is suggested to occur by the so-called radical pair mechanism, whereby the electron spins of radical pairs formed in the course of cryptochrome activation can be manipulated by external magnetic fields. However, the identity of the magnetosensitive step and of the magnetically sensitive radical pairs remains a matter of debate. Here we investigate the effect of a static magnetic field of 500 µT (10× earth's magnetic field) which was applied in the course of a series of iterated 5 min blue light/10 min dark pulses. Under the identical pulsed light conditions, cryptochrome responses were enhanced by a magnetic field even when exposure was provided exclusively in the 10 min dark intervals. However, when the magnetic stimulus was given exclusively during the 5 min light interval, no magnetic sensitivity could be detected. This result eliminates the possibility that magnetic field sensitivity could occur during forward electron transfer to the flavin in the course of the cryptochrome photocycle. By contrast, radical pair formation during cryptochrome flavin reoxidation would occur independently of light, and continue for minutes after the cessation of illumination. Our results therefore provide evidence that a magnetically sensitive reaction is entwined with dark-state processes following the cryptochrome photoreduction step.

Significant cardiac disease complicating Graves' disease in previously healthy young adults.

SUMMARY: Graves' disease is associated with tachydysrythmia, cardiac ischaemia and cardiomyopathy - all uncommon in young adults without previous cardiac disease. We present three young individuals who developed cardiac complications after periods of uncontrolled Graves' disease. Subject 1: A 34-year-old female had severe thyrotoxic symptoms for weeks. Investigations showed fT4: 98.4 (11-25 pmol/L), fT3: 46.9 (3.1-6.8 pmol/L), TSH <0.01 (0.27-4.2 mU/L) and thyrotrophin receptor antibody (TRAb): 34.8 (<0.9 U//l). She had appropriate treatment but several weeks later she became breathless despite improving thyroid function. Echocardiography showed a pericardial effusion of 2.9 cm. She responded well to steroids and NSAIDs but developed active severe Graves' orbitopathy after early total thyroidectomy. Subject 2: A 28-year-old male developed thyrotoxic symptoms (fT4: 38 pmol/L, fT3: 13.9 pmol/L, TSH <0.01 (for over 6 months) and TRAb: 9.3 U/L). One month after starting carbimazole, he developed acute heart failure (HF) due to severe dilated cardiomyopathy - EF 10-15%. He partially recovered after treatment - EF 28% and had early radioiodine treatment. Subject 3: A 42-year-old woman who had been thyrotoxic for several months (fT4: 54.3; fT3 >46.1; TSH <0.01; TRAb: 4.5) developed atrial fibrillation (AF) and heart failure. Echocardiography showed cardiomegaly - EF 29%. She maintains sinus rhythm following early total thyroidectomy (EF 50%). Significant cardiac complications may occur in previously fit young adults, who have had uncontrolled Graves' disease for weeks to months. Cardiac function recovers in the majority, but early definitive treatment should be discussed to avoid Graves' disease relapse and further cardiac decompensation. LEARNING POINTS: Cardiac complications of Graves' disease are uncommon in young adults without previous cardiac disease. These complications may however occur if Graves' disease had been poorly controlled for several weeks or months prior to presentation. Persistent symptoms after adequate control should alert clinicians to the possibility of cardiac disease. Specific treatment of Graves' disease and appropriate cardiac intervention results in complete recovery in the majority and carries a good prognosis. Early definitive treatment should be offered to them to prevent cardiac decompensation at times of further relapse.

Managing thymic enlargement in Graves' disease.

Thymic enlargement (TE) in Graves' disease (GD) is often diagnosed incidentally when chest imaging is done for unrelated reasons. This is becoming more common as the frequency of chest imaging increases. There are currently no clear guidelines for managing TE in GD. Subject 1 is a 36-year-old female who presented with weight loss, increased thirst and passage of urine and postural symptoms. Investigations confirmed GD, non-PTH-dependent hypercalcaemia and Addison's disease (AD). CT scans to exclude underlying malignancy showed TE but normal viscera. A diagnosis of hypercalcaemia due to GD and AD was made. Subject 2, a 52-year-old female, was investigated for recurrent chest infections, haemoptysis and weight loss. CT thorax to exclude chest malignancy, showed TE. Planned thoracotomy was postponed when investigations confirmed GD. Subject 3 is a 47-year-old female who presented with breathlessness, chest pain and shakiness. Investigations confirmed T3 toxicosis due to GD. A CT pulmonary angiogram to exclude pulmonary embolism showed TE. The CT appearances in all three subjects were consistent with benign TE. These subjects were given appropriate endocrine treatment only (without biopsy or thymectomy) as CT appearances showed the following appearances of benign TE - arrowhead shape, straight regular margins, absence of calcification and cyst formation and radiodensity equal to surrounding muscle. Furthermore, interval scans confirmed thymic regression of over 60% in 6 months after endocrine control. In subjects with CT appearances consistent with benign TE, a conservative policy with interval CT scans at 6 months after endocrine control will prevent inappropriate surgical intervention. Learning points: Chest imaging is common in modern clinical practice and incidental anterior mediastinal abnormalities are therefore diagnosed frequently. Thymic enlargement (TE) associated with Graves' disease (GD) is occasionally seen in view of the above. There is no validated strategy to manage TE in GD at present. However, CT (or MRI) scan features of the thymus may help characterise benign TE, and such subjects do not require thymic biopsy or surgery at presentation. In them, an expectant 'wait and see' policy is recommended with GD treatment only, as the thymus will show significant regression 6 months after endocrine control.

Triggering of the thumb with de Quervain's stenosing tendovaginitis.

Triggering with de Quervain's stenosing tenosynovitis has rarely been mentioned since de Quervain's original description. Either or both the abductor pollicis longus and extensor pollicis brevis tendons may be responsible. Without detailed examination testing specifically for triggering, the entity may be overlooked. We have encountered nine patients with triggering in the first dorsal compartment. The five with surgical release had complete resolution of symptoms; the four treated nonoperatively have improved but still have symptoms. Triggering may represent a more severe form of de Quervain's tendovaginitis.