Quantitative assessment of the relevance of organic-anion-transporting-polypeptide 1B1 and 2B1 polymorphisms in fexofenadine pharmacokinetic variants via pharmacometrics / 药物分析学报

Fexofenadine is useful in various allergic disease treatment.However,the pharmacokinetic variability information and quantitative factor identification of fexofenadine are very lacking.This study aimed to verify the validity of previously proposed genetic factors through fexofenadine population pharmaco-kinetic modeling and to explore the quantitative correlations affecting the pharmacokinetic variability.Polymorphisms of the organic-anion-transporting-polypeptide(OATP)1B1 and 2B1 have been proposed to be closely related to fexofenadine pharmacokinetic diversity.Therefore,modeling was performed using fexofenadine oral exposure data according to the OATP1B1-and 2B1-polymorphisms.OATP1B1 and 2B1 were identified as effective covariates of clearance(CL/F)and distribution volume(V/F)-CL/F,respectively,in fexofenadine pharmacokinetic variability.CL/F and average steady-state plasma con-centration of fexofenadine differed by up to 2.17-and 2.20-folds,respectively,depending on the OATP1B1 polymorphism.Among the individuals with different OATP2B1 polymorphisms,the CL/F and V/F differed by up to 1.73-and 2.00-folds,respectively.Ratio of the areas under the curves following single-and multiple-administrations,and the cumulative ratio were significantly different between OATP1B1-and 2B1-polymorphism groups.Based on quantitative prediction comparison through a model-based approach,OATP1B1 was confirmed to be relatively more important than 2B1 regarding the degree of effect on fexofenadine pharmacokinetic variability.Based on the established pharmacokinetic-pharmacodynamic relationship,the difference in fexofenadine efficacy according to genetic poly-morphisms of OATP1B1 and 2B1 was 1.25-and 0.87-times,respectively,and genetic consideration of OATP1B1 was expected to be important in the pharmacodynamics area as well.This population phar-macometrics study will be a very useful starting point for fexofenadine precision medicine.

Evaluating the Outcome of Multi-Morbid Patients Cared for by Hospitalists: a Report of Integrated Medical Model in Korea

BACKGROUND: The lack of medical personnel has led to the employment of hospitalists in Korean hospitals to provide high-quality medical care. However, whether hospitalists' care can improve patients' outcomes remains unclear. We aimed to analyze the outcome in patients cared for by hospitalists. METHODS: A retrospective review was conducted in 1,015 patients diagnosed with pneumonia or urinary tract infection from March 2017 to July 2018. After excluding 306 patients, 709 in the general ward who were admitted via the emergency department were enrolled, including 169 and 540 who were cared for by hospitalists (HGs) and non-hospitalists (NHGs), respectively. We compared the length of hospital stay (LOS), in-hospital mortality, readmission rate, comorbidity, and disease severity between the two groups. Comorbidities were analyzed using Charlson comorbidity index (CCI). RESULTS: HG LOS (median, interquartile range [IQR], 8 [5–12] days) was lower than NHG LOS (median [IQR], 10 [7–15] days), (P < 0.001). Of the 30 (4.2%) patients who died during their hospital stay, a lower percentage of HG patients (2.4%) than that of NHG patients (4.8%) died, but the difference between the two groups was not significant (P = 0.170). In a subgroup analysis, HG LOS was shorter than NHG LOS (median [IQR], 8 [5–12] vs. 10 [7–16] days, respectively, P < 0.001) with CCI of ≥ 5 points. CONCLUSION: Hospitalist care can improve the LOS of patients, especially those with multiple comorbidities. Further studies are warranted to evaluate the impact of hospitalist care in Korea.

Acute toxicity and cytotoxicity evaluation of Dendrobium moniliforme aqueous extract in vivo and in vitro / 한국실험동물학회지

Dendrobium moniliforme (L.) Sw., an herb of the Orchidaceae family, has long been used in traditional medicine to strengthen bones, nourish the stomach, and promote the production of bodily fluid. Recently, polysaccharides isolated from Dendrobium have been used in functional foods and nutraceutical products. A traditional method to process Dendrobium is to soak fresh stems in an ethanol solution, which is the most important factor to ensure high yields of aqueous-extractable polysaccharides. The present study was carried out to investigate the potential acute toxicity of D. moniliforme aqueous extract (DMAE), by a single oral dose in Sprague-Dawley rats. The test article was orally administered once by gavage to male and female rats at doses of 0, 2,500, and 5,000 mg/kg body weight (n=5 male and female rats for each dose). Throughout the study period, no treatment-related deaths were observed and no adverse effects were noted in clinical signs, body weight, food consumption, serum biochemistry, organ weight, or gross findings at any dose tested. The results show that a single oral administration of DMAE did not induce any toxic effects at a dose below 5,000 mg/kg in rats, and the minimal lethal dose was considered to be over 5,000 mg/kg body weight for both sexes. With respect to cytotoxicity, the cell viability of human embryonic kidney (HEK293) cells was less than 50% when the cells were treated with 10 mg/mL aqueous extract for 24 h.

Simultaneous Manifestation of Gangliocytic Paraganglioma and Heterotopic Pancreas of Ampulla of Vater Treated by Endoscopic Resection / 대한췌담도학회지

Gangliocytic paraganglioma is an uncommon tumor of digestive system that is usually found in the second portion of duodenum. It is generally considered benign tumor, although few reports of local recurrences and regional lymph node metastases have been made. Gangliocytic paraganglioma is characterized by its histologic pattern including ganglion cells, spindle cells and epithelioid cells. Heterotopic pancreas, also known as ectopic pancreas, is a pancreatic tissue appeared outside of its normal location lacking anatomic or vascular connection with the pancreas. In duodenum, it is a relatively unusual lesion that may be found incidentally during surgery or endoscopy. We present a case of 39-year-old woman with gangliocytic paraganglioma combined with heterotopic pancreas in the ampulla of Vater successfully treated by endoscopic resection.

Simultaneous Manifestation of Gangliocytic Paraganglioma and Heterotopic Pancreas of Ampulla of Vater Treated by Endoscopic Resection / 대한췌담도학회지

Gangliocytic paraganglioma is an uncommon tumor of digestive system that is usually found in the second portion of duodenum. It is generally considered benign tumor, although few reports of local recurrences and regional lymph node metastases have been made. Gangliocytic paraganglioma is characterized by its histologic pattern including ganglion cells, spindle cells and epithelioid cells. Heterotopic pancreas, also known as ectopic pancreas, is a pancreatic tissue appeared outside of its normal location lacking anatomic or vascular connection with the pancreas. In duodenum, it is a relatively unusual lesion that may be found incidentally during surgery or endoscopy. We present a case of 39-year-old woman with gangliocytic paraganglioma combined with heterotopic pancreas in the ampulla of Vater successfully treated by endoscopic resection.

A Case of Transgastrostomal Endoscopy to Diagnose and Treat Gastric Ulcer Bleeding

Gastrostomy tube feeding is a common method to provide nutritional support for patients with inadequate oral intake. Gastrostomy tube feeding carries the risk for various complications, with percutaneous hemorrhage being a major complication. Gastric ulcer bleeding is a rare complication in these patients and few researchers have reported such events. There has been no case report of gastric ulcer bleeding diagnosed and treated by endoscopy through a mature gastrostomy tract in Korea. We describe here a case in which gastric ulcer bleeding was diagnosed and treated by a transgastrostomal endoscopy.

Myelodysplastic Syndrome and Minimal Change Nephrotic Syndrome treated with Steroid Challenge / 대한내과학회지

Glomerulonephritis associated with malignancy is deemed to be paraneoplastic glomerulonephritis. Myelodysplastic syndrome (MDS) is a group of heterogeneous clonal hematopoietic stem cell disorders characterized by impaired hematopoietic cell differentiation and cytopenia. The pathophysiology of MDS is thought to be immune-mediated in part. A few reports have documented various forms of glomerulonephritis in patients with MDS and suggested that immune dysregulation is important in the development of paraneoplastic glomerulonephritis. Here, we report a patient with MDS and refractory anemia with excess blast-2 accompanied by minimal change nephrotic syndrome. The patient was treated with prednisolone, and the nephrotic-range proteinuria and pancytopenia improved markedly.

Spontaneous coronary artery dissection by intravascular ultrasound in a patient with myocardial infarction

Spontaneous coronary artery dissection is a rare cause of acute coronary syndrome and sudden cardiac death. The incidence, causes, pathogenesis, and treatment have not been defined clearly, but spontaneous coronary artery dissection should be considered in young patients without major cardiovascular risk factors or in patients in the peripartum period who present with acute coronary syndrome. The treatment is often challenging. Medical treatment is usually considered, and percutaneous coronary intervention or coronary artery bypass surgery may be possible in some patients. We herein report two cases of middle-aged males with myocardial infarction who were treated with percutaneous coronary angioplasty.

Transient J-Wave Appearance in the Inferior-Lateral Leads during Electrical Storm in a Patient with Brugada Syndrome

A 67-year-old male patient was admitted with an abrupt sudden cardiac death. He represented with an extreme electrical storm of 30 times of ventricular fibrillation (VF) episodes on one day. External shocks were performed to terminate VF. Transient J-wave in the inferior-lateral leads and Brugada electrocardiography pattern on the right precordial leads appeared during the electrical storm. And J-wave disappeared after the termination of electrical storm. We report a case of the appearance of J-wave during electrical storm in a patient with Brugada syndrome.

Successful coronary stent retrieval from the ascending aorta using a gooseneck snare kit

Coronary stent dislodgement is a rare complication of percutaneous coronary intervention. We report a case of stent dislodgement in the ascending thoracic aorta. The stent was mechanically distorted in the left circumflex artery (LCX) while being delivered to the proximal LCX lesion. The balloon catheter was withdrawn, but the stent with the guide wire was remained in the ascending thoracic aorta. The stent was unable to be retrieved into the guide catheter, as it was distorted. A goose neck snare was used successfully to catch the stent in the ascending thoracic aorta and retrieved the stent externally via the arterial sheath.

Two dislodged and crushed coronary stents: treatment of two simultaneously dislodged stents using crushing techniques

Coronary stent dislodgement is a rare complication of percutaneous coronary intervention. We report a rare case of dislodgement of two intracoronary stents. On withdrawal of two balloon catheters, one with a guide wire was mechanically distorted from the left main (LM) to the proximal left anterior descending artery (LAD) while the other was dislodged from the LM to the ostial left circumflex artery. The stent in the LAD could not be retrieved into the guide catheter using a Goose neck snare, because it was caught on a previously deployed stent at the mid LAD. A new stent was quickly deployed from the LM to the proximal LAD, because the patient developed cardiogenic shock. Both stents, including a distorted and elongated stent, were crushed to the LM wall. Stent deployment and crushing may be a good alternative technique to retrieving a dislodged stent.

Application of an Insulin Analogue in Six Hypoglycemia-Prone Hemodialysis Patients with Type 2 Diabetes / 대한내과학회지

Day-to-day insulin requirements often change due to subtle variations in insulin metabolism in patients with type 2 diabetes undergoing hemodialysis. In such cases, intra-hemodialysis hypoglycemia frequently occurs and is a main factor interfering with the delivery of dialysis. As a result, it reduces the quality of life in patients undergoing hemodialysis. The long-acting insulin analogue glargine provides peakless, continuous release over 24 h that approximates a normal basal insulin pattern. Because it has no peak, its use in patients with diabetes undergoing hemodialysis would hypothetically be useful. Specifically, patients would be able to avoid intra-hemodialysis hypoglycemia without the necessity of skipping insulin administration on the day of hemodialysis and achieving adequate glucose control on other days. We recently experienced six cases that switched from treatment with intermediate-acting insulin to a long-acting insulin analogue, which provided better glycemic control by reducing hypoglycemia risk. Limited data are available in the literature concerning insulin analogue usage in patients with diabetes undergoing hemodialysis. Our experience suggests a large-scale prospective investigation is required on this issue.

Complete Atrioventricular Block Associated with Hyponatremia / 대한내과학회지

We report the case of a 77-year-old woman who developed complete atrioventricular (AV) block during an episode of thiazide-induced hyponatremia. She was taking hydrochlorothiazide to treat essential hypertension; she had no definite organic disease of the heart or lungs. Generally, the serum sodium concentration does not have a marked effect on cardiac conduction. However, we experienced a case of complete AV block associated with hyponatremia. This was treated successfully by correcting the electrolyte imbalance. Complete AV block associated with hyponatremia is very rare. To our knowledge, this is the first reported case in Korea.

Pontine Hemorrhage after Surgical Evacuation of Nontraumatic Subdural Hematoma

Duret hemorrhage is characterized by an upper brainstem hemorrhage due to increased intracranial pressure by mass effect such as subdural hematoma or a brain tumor. The anteroposterior elongation and downward displacement of the upper brainstem by transtentorial herniation results in the compression and tearing of the paramedian perforating vessels that feed the upper brainstem tegmentum. The consequent hemorrhage that involves the upper brainstem renders recovery to be almost impossible. Following a tricuspid valve replacement surgery, a 56-year-old woman developed a left fronto-temporo-parietal nontraumatic subdural hematoma resulting in transtentorial herniation of the left mesial temporal lobe. A successful surgical evacuation of the hematoma was done with clinical improvement. Two days later, she was referred to neurology with an aggravated right side weakness, dysarthria, and a newly developed extraocular movement disturbance. A brain CT and MRI showed a pontine hemorrhage. We report a case of pontine hemorrhage, a Duret hemorrhage, after the surgical evacuation of nontraumatic subdural hematoma.

A Case of Idiopathic Intracranial Hypertension Treated with Optic Nerve Sheath Fenestration

Idiopathic intracranial hypertension, a syndrome of obscure origin, occurs particularly in fat adolescent girls and young women. The usual symptoms are headache, blurred vision, a vague dizziness, horizontal diplopia and transient visual obscurations etc., and ophthalmoscopic examination reveals papillederma, due to increased ICP. Visual field testing usually shows slight peripheral constrictions with enlargement of the blind sports. CSF pressure is elevated in the range of 250 to 450 mm of water. Radiological or the other laboratory tests show no specific abnormalities. Treatment for idiopathic intracranial hypertension is focused on early detection and prevention of vision loss, the only permanent morbidity. Many different modes of medical treatment, including weight reduction, repeated lumber puncture, corticosteroids, diuretics, glycerol or carbonic anhydrase inhibitors, have successfully been tried up to 90% of the patients. In the remaining patients, particularly in those with measurable impairment of vision that does not respond to conventinal medical therapies, surgical procedure should be considered. We report a case of idiopathic intracranial hypertension successfully treated with optic nerve sheath fenestration.