Long-Term Follow-Up Over 16 Years for Pituitary Hyperplasia Due to Primary Hypothyroidism With Positive Thyroid Stimulation Blocking Antibody: A Case Report.

Primary hypothyroidism is a known risk factor for pituitary hyperplasia, which develops symptoms due to compression of the optic chiasma and increased intracranial pressure. As pituitary hyperplasia is known to improve after levothyroxine replacement therapy, there are no reports of a long clinical course of pituitary hyperplasia due to primary hypothyroidism. We describe a case of follow-up over 16 years for pathologically diagnosed pituitary hyperplasia due to primary hypothyroidism with positive thyroid stimulation blocking antibody. Repeated enlargement and shrinkage were confirmed, but observations also suggested that the pituitary gland did not always return to normal size.

Antithyroid arthritis syndrome caused by methimazole in a patient with Graves' disease.

Summary: This is a report on antithyroid arthritis syndrome (AAS) which is a rare adverse effect of antithyroid agents. AAS presents with severe symptoms including myalgia, arthralgia, arthritis, fever, and skin eruption due to the use of antithyroid agents. We encountered a 55-year-old woman with severe pain in the hand and forearm and arthralgia in multiple joints, including the knee, ankle, hand, and wrist on day 23 after initiation of methimazole (MMI) for Graves' disease. Blood tests revealed elevated inflammation markers such as C-reactive protein and interleukin-6, and magnetic resonance imaging of the hands confirmed inflammation findings. After withdrawing MMI on day 25, symptoms showed a tendency toward improvement. Afterwards, inflammation markers also dropped to an almost normal range. In addition to the above findings, the absence of anti-neutrophil cytoplasmic antibodies and most vasculitis symptoms such as nephritis, skin, or pulmonary lesions led to the diagnosis of AAS. A resolution of symptoms, except for mild arthralgia in the second to fourth fingers of the right hand, was observed 61 days after discontinuation of MMI. Although the pathogenesis is unclear, the positive drug lymphocyte stimulation test for MMI and the several weeks before the onset of AAS suggested involvement of a type IV allergic reaction. Based on a discussion of definitive treatment for Graves' disease, radioactive iodine ablation with 131I, which was selected by the patient, was performed and improved her thyroid function. Our case demonstrates the importance of awareness regarding AAS, which is a rare and under-recognized, but life-threatening adverse effect of antithyroid agents. Learning points: Clinicians should be aware of the possibility of developing antithyroid arthritis syndrome (AAS) in patients treated with antithyroid medications, which can lead to severe migratory polyarthritis. Prompt cessation of the antithyroid agent is essential for the resolution of AAS. Anti-neutrophil cytoplasmic antibody (ANCA) negativity is needed to differentiate from antithyroid agent-induced ANCA-associated vasculitis, which shows arthritis similar to AAS.

Invasive Mucinous Adenocarcinoma with Acute Respiratory Distress Syndrome Diagnosed by Autopsy Findings.

We herein report a fatal case of invasive mucinous adenocarcinoma (IMA) with acute respiratory distress syndrome (ARDS) diagnosed based on autopsy findings. A 76-year-old man presented with severe respiratory discomfort on admission. Computed tomography (CT) revealed a peripheral distribution of consolidation. Although his respiratory status improved after steroid therapy, re-exacerbation occurred, and the patient died on day 131. A bronchoscopic lung biopsy had shown organizing pneumonia, but a post-mortem examination surprisingly revealed IMA with organizing pneumonia. IMA presenting with ARDS as the first symptom is extremely rare.

Edoxaban Dosing Time Affects Blood Coagulation Inhibition in Rats.

Coagulation-fibrinolytic system activity shows daily rhythmicity, with hypercoagulability in the morning and hypocoagulability in the evening. Consequently, the efficacy of anticoagulants may be influenced by their dosing time. Edoxaban, a selective inhibitor of the active form of coagulation factor X (FXa), is taken orally once daily, but the optimal dosing time is unknown. This study evaluated the dosing time-dependent effects of edoxaban on coagulation activity and thrombus formation in rats. Edoxaban (10 mg/kg) or vehicle was administered to Wistar rats at zeitgeber time (ZT)-2 (beginning of the light phase) or ZT14 (beginning of the dark phase), followed by blood collection at ZT4, ZT10, ZT16, or ZT22, to measure the activity of coagulation factors and edoxaban concentrations, or followed by inferior vena cava ligations at ZT4 or ZT16, to assess the efficacy of edoxaban against thrombus formation. Coagulation FX activity was high during the light phase, and a single dose of edoxaban administered at ZT2 inhibited FX activity and thrombus formation more potently compared with the same dose administered at ZT14. The inhibitory effects during the light phase could be attributed, at least in part, to the high blood concentration of edoxaban achieved by dosing at ZT2. Morning dosing of edoxaban leads to a high blood concentration of the drug during the morning hours and thus may better counteract the hypercoagulability and hypofibrinolytic activity characteristic of the morning hours. Optimizing the dosing time may contribute to improving the efficacy of edoxaban.

Folding of the Cerebral Cortex Requires Cdk5 in Upper-Layer Neurons in Gyrencephalic Mammals.

Folds in the cerebral cortex in mammals are believed to be key structures for accommodating increased cortical neurons in the cranial cavity. However, the mechanisms underlying cortical folding remain largely unknown, mainly because genetic manipulations for the gyrencephalic brain have been unavailable. By combining in utero electroporation and the CRISPR/Cas9 system, we succeeded in efficient gene knockout of Cdk5, which is mutated in some patients with classical lissencephaly, in the gyrencephalic brains of ferrets. We show that Cdk5 knockout in the ferret cerebral cortex markedly impaired cortical folding. Furthermore, the results obtained from the introduction of dominant-negative Cdk5 into specific cortical layers suggest that Cdk5 function in upper-layer neurons is more important for cortical folding than that in lower-layer neurons. Cdk5 inhibition induced severe migration defects in cortical neurons. Taken together, our findings suggest that the appropriate positioning of upper-layer neurons is critical for cortical folding.

Concise entry to chiral 5-(4-hydroxybutyl)-2(5H)-furanone via HTIB-mediated novel oxidative fragmentation: formal total synthesis of (+)-dubiusamine A.

The concise synthesis of 5-(4-hydroxybutyl)-2(5H)furanone has been accomplished from 9-oxabicyclo[4.2.1]non-7-en-1-ol on the basis of HTIB [PhI(OH)OTs, a.k.a. Koser's reagent]-mediated novel oxidative fragmentation. Chiral (-)-(R)-5-(4-hydroxy-butyl)-2(5H)-furanone (>99% ee) was used for the formal total synthesis of (+)-dubiusamine A (1).

Concise entry to both enantiomers of 8-oxabicyclo[3.2.1]oct-3-en-2-one based on novel oxidative etherification: formal synthesis of (+)-sundiversifolide.

Both enantiomers of 8-oxabicyclo[3.2.1]oct-3-en-2-one (6) have been synthesized from 4-hydroxycyclohept-2-enone (3) on the basis of a novel oxidative cyclo-etherification using PhI(OH)OTs (Koser's reagent). (-)-(1S,5R)-8-Oxabicyclo[3.2.1]oct-3-en-2-one [(-)-6, 95% ee] was expeditiously transformed to (+)-sundiversifolide (1).