A selective and sensitive competitive enzyme-linked immunosorbent assay (ELISA) method was developed and validated for the quantification of erlotinib in 50μL of samples of human serum. Anti-erlotinib serum was obtained by immunizing mice with an antigen conjugated with bovine serum albumin and 3,4-bis(2-methoxyethoxy)benzoic acid using the N-succinimidyl ester method. Enzyme labeling of erlotinib with horseradish peroxidase was similarly performed using 3,4-bis(2-methoxyethoxy)benzoic acid. A simple competitive ELISA for erlotinib was developed using the principle of direct competition between erlotinib and the enzyme marker for anti-erlotinib antibody, which had been immobilized on the plastic surface of a microtiter plate. Serum erlotinib concentrations lower than 40 ng/mL were reproducibly measurable using the ELISA. This ELISA was specific to erlotinib and showed very slight cross-reactivity (6.7％) with a major metabolite, O-desmethyl erlotinib. Using this assay, drug levels were easily measured in the blood of mice after oral administration of erlotinib at a single dose of 30 mg/kg. ELISA should be used as a valuable tool for therapeutic drug monitoring and in pharmacokinetic studies of erlotinib.

Surgical treatment of two abdominal and two thoracic aneurysms in hemodialysis patients were performed from 1991 to 1993. Two elective cases survived, but two emergency cases died. The causes of death were PMI and respiratory failure. Ruptured aneurysms are critical and probably result in higher mortality and morbidity than elective replacement of aneurysms. In view of the documented risk of rupture and current operative risk, we believe that elective surgical treatment of aneurysm is a much better treatment than following the aneurysms until they produce symptoms or significantly enlarge.

The sudden development of cyanotic lesions on the foot and toes may be a result of atheroembolic disease referred to as “blue toe syndrome”. During the last 7 years, 10 patients, consisting of 7 men and 3 women, were treated for ischemia of the toes of varied severity. The patients' ages ranged from 58 to 85 years (mean 73 years). Five patients had lesions on both legs and 5 on one leg. Contrast-enhanced abdominal CT scan revealed atherosclerotic changes of the abdominal aorta concomitant with intramural thrombus in every examined case. Four patients were treated medically and 4 underwent surgery consisting of replacement of the abdominal aorta in 3 and minor amputation of the toes in the other case. Two other patients developed acute renal failure within two months after the diagnosis of blue toe syndrome and succumbed to either heart failure or bleeding peptic ulcer. Contrast-enhanced CT scan is important for the diagnosis of blue toe syndrome. Though the prognosis of patients with blue toe syndrome is good in most cases, multiple microembolization to the viscera may cause renal failure and the prognosis of those patients is less favorable. Surgical intervention should be considered if the blue toe syndrome patient has an abdominal aortic aneurysm or history of multiple embolic episodes.

A 54-year-old male with sudden back pain was diagnosed as having acute aortic dissection of Stanford type A. He underwent an aortic arch replacement under the deep hypothermic circulatory arrest and retrograde cerebral perfusion. During retrograde cerebral perfusion, the central venous pressure was maintained at 20mmHg, the perfusion flow rate was 400ml/min and the lowest rectal temperature was 19°C. The duration of retrograde cerebral perfusion was 135 min, but the patient recovered successfully without any evidence of neurological complications. This report suggests that retrograde cerebral perfusion associated with deep hypothermic circulatory arrest has the possibility to prolong the safety time limit of antegrade cerebral circulatory arrest up to 135min.

Porcelain aorta entails a high risk of cerebral as well as systemic embolism. We describe a case of aortic arch aneurysm with a circumferentially calcified aorta. The patient was a 61-year-old man on chronic hemodialysis who received aortic arch replacement. However, since chest CT scan revealed a totally calcified porcelain aorta and heavily calcified axillary artery, axillary artery cannulation was deemed to be contraindicated. On the other hand, possible complications caused by femoral artery cannulation are also well known, such as cerebral embolization. Therefore, transapical aortic cannula was used and aortic arch replacement was performed under deep hypothermic circulatory arrest. The patient was weaned from cardiopulmonary bypass without difficulty and had an uneventful recovery without any neurologic complications.

A 72 year-old man underwent coronary angiography (CAG) with a diagnosis of unstable angina pectoris, and 90% stenosis of the LMT was found. Since idiopathic interstitial pneumonia (IIP) had been diagnosed previously, percutaneous transluminal coronary angioplasty (PTCA) was performed. However, his unstable angina recurred after about 2 months restenosis of the LMT to 90% was shown by CAG, and coronary artery bypass grafting (CABG) was performed. In the preoperative chest X-ray, diffuse granular opacities were seen in both lower lungfields, and Velcro rales were heard by ausculation. A spirogram could not be obtained because of his unstable angina, but the PaO₂ was a reasonable 70mmHg when breathing room air. In consideration of the age of the patient, a double coronary artery bypass grafting using a saphenous vein graft (SVG) was performed to minimize duration of anesthesia. His PaO₂ showed a transient decrease after the end of cardiopulmonary bypass (CPB), but the perioperative hemodynamics and respiratory status were stable and extubation was performed on the 1st postoperative day. No aggravation of his IIP occurred postoperatively and he was discharged on the 29th postoperative day.

A total of 961 patients underwent coronary artery bypass grafting (CABG) between 1982 and 1991, and we investigated perioperative cerebral infarction. The average age of operation in these case was 65±4 years. There was 9 patients with hypertension, 7 with diabetes mellitus and 5 with hyperlipidemia. Concerning cerebral infarction, there were 3 patients with multiple infarction, 6 with infarction of the mid cerebral artery area, 1 with infarction of posterior cerebral artery area, 1 with infarction of posterior cerebral artery area, 1 with infarction of pons and 1 with infarction of the ophthalmic artery. The courses of infarction involved atherosclerosis, hypoperfusion during cardiopulmonary bypass, thrombosis due to arterial fibrillation and thrombus on the left ventricular wall. Three patients who had critical cerebral infarction died after CABG. We consider that avoid perioperative cerebral infarction preoperative atherosclerosis, thrombus and to choose the proper procedure of the operation.

Coronary artery bypass grafting using hypothermic circulatory arrest and ventricular fibrillation without aortic cross clamping in 6 patients with severely calcified aortas is described. The use of hypothermic circulatory arrest or ventricular fibrillation has not been established in coronary artery bypass grafting. We recently used aortic no-touch technique in 6 patients. All patients were supported and cooled with cardiopulmonary bypass, and circulatory arrest was performed in 3 patients. With the exception of one hemodialysis patient, 5 patients survived without neurological deficit. We think the aortic no-touch technique is safe and reliable in coronary artery bypass grafting with severe calcified aortas.

Afatinib is an oral tyrosine kinase inhibitor (TKI) approved for treating advanced non-small cell lung cancer. It is necessary to develop a simple quantification method for TKIs in order to facilitate therapeutic drug monitoring (TDM) in clinical settings. This study sought to develop a simple and sensitive com-petitive enzyme-linked immunosorbent assay (ELISA) to quantify afatinib in plasma for routine phar-macokinetic applications. An anti-afatinib antibody was obtained using (S)-N-4-(3-chloro-4-fluor-ophenyl)-7-(tetrahydrofuran-3-yloxy)-quinazoline-4,6-diamine (CTQD), which has the same sub-structure as afatinib, as a hapten. Enzyme labeling of afatinib with horseradish peroxidase was similarly performed using CTQD. A simple competitive ELISA for afatinib was developed based on the principle of direct competition between afatinib and the enzyme marker for the anti-afatinib antibody, which had been immobilized on the plastic surface of a microtiter plate. Plasma afatinib concentrations below the limit of quantification of 30 pg/mL were reproducibly measurable. Also, the values of plasma afatinib levels measured from 20 patients were comparable with those measured by high-performance liquid chromatography, and there was a strong correlation between the values determined by both methods (Y = 0.976X – 0.207, r = 0.975). As indicated by its specificity and sensitivity, this newly developed ELISA for afatinib is an important tool for TDM and studies of the pharmacokinetics of afatinib.

The rapid spread of COVID-19, which was first reported in Wuhan, China, gave unprecedented impacts to the peoplearound the globe. Since no current established treatments nor medications are available, medical professionals are longing for the effective tools to fight against COVID-19. The true value of Chinese herbal medicine can be seen under such tough circumstances. The effects of Sanyao Sanfang, containing various naturally occurring phytochemicals were reported from the epicenter of COVID-19 in China. The distinctive feature of the Sanyao Sanfang is its ability to strengthen vitality of the body and improved resistance against invasive attacks by viruses and microbes. It also promotes activation of the immune system and its recovery to healthy status. It is obvious that the comprehensive effects of the Sanyao Sanfang do not stem from a single substance. Further studies are warranted for clarification of the mechanism and the role of other raw materials, as well as for the improvement of its formulation, efficacy and safety.