KF-1607, a Novel Pan Src Kinase Inhibitor, Attenuates Obstruction-Induced Tubulointerstitial Fibrosis in Mice

Src family kinases (SFKs), an important group of non-receptor tyrosine kinases, are suggested to be excessively activated during various types of tissue fibrosis. The present study investigated the effect of KF-1607, an orally active and a newly synthesized Src kinase inhibitor (SKI) with proposed low toxicity, in preventing the progression of renal interstitial fibrosis. Unilateral ureteral obstruction (UUO) surgery was performed in 6-week-old male C57BL/6 mice to induce renal interstitial fibrosis. Either KF-1607 (30 mg/kg, oral gavage) or PP2 (2 mg/kg, intraperitoneal injection), a common experimental SKI, was administered to mice for seven days, started one day prior to surgery. UUO injury-induced SFK expression, including Src, Fyn, and Lyn kinase. SFK inhibition by KF-1607 prevented the progression of tubular injury in UUO mice, as indicated by decreases in albuminuria, urinary KIM-1 excretion, and kidney NGAL protein expression. Renal tubulointerstitial fibrosis was attenuated in response to KF-1607, as shown by decreases in α-SMA, collagen I and IV protein expression, along with reduced Masson’s trichrome and collagen-I staining in kidneys. KF-1607 also inhibited inflammation in the UUO kidney, as exhibited by reductions in F4/80 positive-staining and protein expression of p-NFκB and ICAM. Importantly, the observed effects of KF-1607 were similar to those of PP2. A new pan Src kinase inhibitor, KF-1607, is a potential pharmaceutical agent to prevent the progression of renal interstitial fibrosis.

Genotoxicity in Patients on Long-term Proton Pump Inhibitor Therapy in Korea: A Nested Case-control, Prospective, Pilot Study

Background/Aims@#Although proton pump inhibitors (PPIs) remain a mainstay for the suppression of gastric acid secretion, long-term PPI use is associated with side effects. However, the genotoxicity associated with long-term PPI use is unclear. @*Materials and Methods@#This prospective observational pilot study enrolled patients who had been on PPIs for >1 year and healthy controls from July 2015 to August 2016. The subjects completed self-report questionnaires pertaining to their drug and medical history, and only those with no medical history and a ≥2-year wash-out period (for drugs other than PPIs) were included. We collected peripheral-blood lymphocytes from long-term PPI users and healthy controls and analyzed the genotoxicity by using the cytokinesis-block micronucleus cytome assay; we also determined the fasting serum levels of pyridoxine, folate, cobalamin, and homocysteine. @*Results@#Ten long-term PPI users and 40 healthy control subjects were enrolled. The median serum pyridoxine, folate, cobalamin, and homocysteine levels were not significantly different between the groups. The median frequencies of micronuclei (MNi), nucleoplasmic bridges (NPBs), and nuclear buds (Nbuds) per 1,000 binucleated cells, in long-term PPI users and healthy controls, were 30.3 and 16.3 (P<0.005), 2.5 and 1.8 (P<0.005), and 9.3 and 5.0 (P<0.005), respectively. Even after adjustment for confounding factors, the OR of the MNi, NPBs, and Nbuds for long-term PPI users compared with healthy control subjects were 14.1 (P<0.001), 2.0 (P=0.001), and 1.3 (P=0.3), respectively. @*Conclusions@#Long-term PPI use was significantly associated with an increased risk of genotoxicity after adjustment for age, sex, body mass index, medical history, drug history, and the serum levels of vitamins.

Paired Primary and Metastatic Tumor Analysis of Somatic Mutations in Synchronous and Metachronous Colorectal Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Although the mutation status of KRAS is highly concordant in primary and metastatic lesions, it has not been generalized to other major pathway genes. MATERIALS AND METHODS: In this study, 41 genes were evaluated and the mutational profiles were compared in 46 colorectal cancer patients with paired surgical specimens of primary and metastatic lesions: synchronous (n=27) and metachronous (n=19) lesions. A high-throughput mass spectrometry-based genotyping platform validated by orthogonal chemistry, OncoMap v.4.4, was used to evaluate the formalin-fixed, paraffin-embedded surgical specimens. The patients’ demographics, tumor characteristics, and microsatellite instability status were analyzed by a retrospective chart review. RESULTS: In this study,with OncoMap, mutationswere identified in 80.4% of patientswith the following frequency: KRAS (39.1%), TP53 (28.3%), APC (28.3%), PIK3CA (6.5%), BRAF (6.5%), and NRAS (4.3%). Although 19.6% (9/46) of the patients showed no gene mutations, 43.5% (20/46) and 37.0% (17/46) had mutations in one and two or more genes, respectively. The synchronous and metachronous lesions showed similar mutational profiles. Paired samples between primary and metastatic tumors differed in 7.4% (2/27) and 10.5% (2/19) for synchronous and metachronous according to OncoMap. CONCLUSION: These findings indicate the major pathway genes, including KRAS, TP53, APC, PIK3CA, BRAF, and NRAS, are often concordant between the primary and metastatic lesions regardless of the temporal relationship of metastasis.

Recurrent Auricular Keloids during Pregnancy

No abstract available.

The Impact of Inosine Triphosphatase Variants on Hemoglobin Level and Sustained Virologic Response of Chronic Hepatitis C in Korean

Two variants of the inosine triphosphatase (ITPA: rs1127354, rs7270101) gene cause ITPA deficiency and protect against the hemolytic toxicity of ribavirin. We investigated the clinical significance of ITPA variants in Korean patients treated with pegylated interferon (PEG-IFN) plus ribavirin. Of the 133 patients, 108 were CC and 25 were non-CC at rs1127354 (groups A and B, respectively). On the other hand, at rs7270101 all 133 were AA. The mean values of Hemoglobin (Hgb) after 4, 8, and 12 weeks of treatment in groups A and B were 12.2 and 14.0, 11.8 and 13.2, and 11.5 and 12.9, respectively (P=0.001, 0.036, 0.036). Sustained virologic response (SVR) was achieved in 67.8% (40/59) of genotype 1 patients and in 75% (27/36) of non-genotype 1 patients. Regarding ITPA variants, SVR was achieved by 66% and 80% of genotype 1 (P=0.282), and by 78% and 71% (P=0.726) of non-genotype 1. SVR was not significantly different in groups A and B. In conclusion, non-CC at rs1127354 without involvement of rs7270101 is strongly associated with protection from ribavirin-induced anemia, however, ITPA genotype is not associated with SVR.

Adrenal Metastasis from Hepatocellular Carcinoma without Intrahepatic Recurrence after Hepatic Resection / 대한소화기학회지

Although the adrenal gland is a common site of metastasis from hepatocellular carcinoma (HCC), adrenal metastases are rarely seen in clinical practice because of its lower metastatic potential compared to the other malignancies. Adrenal metastases usually were detected at the time of diagnosis of primary HCC or simultaneously with intrahepatic recurrence after curative management of HCC. It is very rare that only metastatic HCC is detected without evidence of intrahepatic recurrence. Hereby, we report two cases of adrenal metastasis from HCC without intrahepatic recurrence after hepatic resection.

A Case of Septic Shock by Prevotella Species associated with Acute Periapical Abscess

A healthy 34-year-old man was admitted to the intensive care unit through the emergency room with a drowsy mentality and severe chilling. Following a diagnosis of septic shock of unknown origin, the patient was treated with broad spectrum antibiotics and massive hydration. After recovery of consciousness, he complained of a severe toothache that originated from the right lower teeth. Under dental consultation, he was diagnosed as having an acute periapical abscess of the right mandibular first molar. The patient underwent extraction and cyst enucleation. Gram negative bacilli isolated from blood culture on day 5 after admission were identified as Prevotella species. After receiving antibiotic treatment and undergoing dental procedures, the patient made a full recovery. We report on a case of septic shock due to infection by Prevotella species in association with an acute periapical abscess.

Supernumerary Nostril: A Case Report

PURPOSE: Supernumerary nostril, also known as triple nostril or accessory nostril, is one of the extremely rare congenital nasal deformities which includes an additional nostril. Since Lindsey reported the first case of a supernumerary nostril, only 34 cases of supernumerary nostril have been reported world widely. And there was no any domestic case. In the present case, we described a case of supernumerary nostril and reviewed all the literature cases of supernumerary nostril. METHODS: A 10-month-old female patient visited to the authors with an additional nostril located above her right nostril, which had been present since birth. Antenatal history was uneventful and the infant's birth was normal. On physical examination there were no other abnormalities and additional nostril was communicating with ipsilateral normal nasal cavity. We performed fistulectomy and local flap for the correction. RESULTS: After 7 months postoperatively, the patient was doing well. The functional outcome was excellent and the cosmetic result was satisfactory. During the long term follow-up for 8 years, there were no specific problems. CONCLUSION: In supernumerary nostril, preoperative evaluation of other abnormalities is very important and we advocate that corrective surgery can be performed at an early age for patient's psychosocial development.

Supernumerary Nostril: A Case Report

PURPOSE: Supernumerary nostril, also known as triple nostril or accessory nostril, is one of the extremely rare congenital nasal deformities which includes an additional nostril. Since Lindsey reported the first case of a supernumerary nostril, only 34 cases of supernumerary nostril have been reported world widely. And there was no any domestic case. In the present case, we described a case of supernumerary nostril and reviewed all the literature cases of supernumerary nostril. METHODS: A 10-month-old female patient visited to the authors with an additional nostril located above her right nostril, which had been present since birth. Antenatal history was uneventful and the infant's birth was normal. On physical examination there were no other abnormalities and additional nostril was communicating with ipsilateral normal nasal cavity. We performed fistulectomy and local flap for the correction. RESULTS: After 7 months postoperatively, the patient was doing well. The functional outcome was excellent and the cosmetic result was satisfactory. During the long term follow-up for 8 years, there were no specific problems. CONCLUSION: In supernumerary nostril, preoperative evaluation of other abnormalities is very important and we advocate that corrective surgery can be performed at an early age for patient's psychosocial development.

Herpes Simplex Virus Infection after Corrective Rhinoplasty through External Approach: Two Case Reports

PURPOSE: Eczema herpeticum, caused by herpes simplex virus, is an infectious disease involving skin and internal organs. Varieties of physiologic, psychosocial, or environmental stress reactivate reservoir virus which exists in the trigeminal nerve ganglia. Authors report rare cases of nasal eczema herpeticum following corrective rhinoplasty. METHODS: First case, 22-year-old female underwent corrective rhioplasty through an external approach in a local clinic. She developed progressive and painful erythema, nodules and vesicles on nose on the 9th day postoperatively. This unfamiliar lesion lead to a misdiagnosis as a bacterial infection, and had accelerated its progress to the trigeminal innervation of the nasal unit. Second case, a 23-year-old female underwent corrective rhinoplasty by external lateral osteotomy. Ten days after the surgery, disruption occurred on the external osteotomy site, and the ulceration gradually worsened. The surgeon misdiagnosed it as secondary bacterial infection and only an antibacterial agent was applied. RESULTS: Both cases were healed effectively without any complication with proper wound dressing and antiviral therapy, and show no sequelae during an 8-month follow-up period. CONCLUSION: Eczema herpeticum is rare in the field of plastic surgery, but it should be kept in mind that secondary bacterial infections may lead to serious complications such as full-thickness skin loss. Thus, acknowledgement of the patient's past history regarding perioral or intraoral lesion may provide the surgeon with the possible expectancy of eczema herpeticum. Thus, if anyone develops eczema herpeticum, following facial plastic surgery, early diagnosis and immediate proper antiviral therapy will allow fast recovery without serious complications.

Herpes Simplex Virus Infection after Corrective Rhinoplasty through External Approach: Two Case Reports

PURPOSE: Eczema herpeticum, caused by herpes simplex virus, is an infectious disease involving skin and internal organs. Varieties of physiologic, psychosocial, or environmental stress reactivate reservoir virus which exists in the trigeminal nerve ganglia. Authors report rare cases of nasal eczema herpeticum following corrective rhinoplasty. METHODS: First case, 22-year-old female underwent corrective rhioplasty through an external approach in a local clinic. She developed progressive and painful erythema, nodules and vesicles on nose on the 9th day postoperatively. This unfamiliar lesion lead to a misdiagnosis as a bacterial infection, and had accelerated its progress to the trigeminal innervation of the nasal unit. Second case, a 23-year-old female underwent corrective rhinoplasty by external lateral osteotomy. Ten days after the surgery, disruption occurred on the external osteotomy site, and the ulceration gradually worsened. The surgeon misdiagnosed it as secondary bacterial infection and only an antibacterial agent was applied. RESULTS: Both cases were healed effectively without any complication with proper wound dressing and antiviral therapy, and show no sequelae during an 8-month follow-up period. CONCLUSION: Eczema herpeticum is rare in the field of plastic surgery, but it should be kept in mind that secondary bacterial infections may lead to serious complications such as full-thickness skin loss. Thus, acknowledgement of the patient's past history regarding perioral or intraoral lesion may provide the surgeon with the possible expectancy of eczema herpeticum. Thus, if anyone develops eczema herpeticum, following facial plastic surgery, early diagnosis and immediate proper antiviral therapy will allow fast recovery without serious complications.

Modified Seven-flap Web Plasty for Incomplete Syndactyly

PURPOSE: Incomplete syndactyly, due to either congenital or acquired, is uncommon. Many different surgical methods have been descirbed. We introduce the modification of seven flap-plasty for incomplete syndactyly and report functional improvement after correction by modified seven flap-plasty without skin graft. MATERIALS AND METHODS: Twelve patients with an incomplete syndactyly who underwent modified seven flap-plasty were analyzed. Age ranged from one to 40-year-old (average age 21). There were 8 males and 4 females, and the degree of syndactyly was near proximal interphalangeal joint. Two different operative methods were performed. Modification I modified two half-Z flaps in parallelogram shape, and modification II modified V flap of V-M flap in Y-V flap. Functional improvements was measured by maximal abduction distance and maximal abduction angle change. RESULTS: All cases were corrected by using the modified seven flap plasty. Flap tip necrosis was found in two cases of severe burn scar patients, but did not require additional surgery. There was no specific complications. Maximal abduction distance was increased in 6 mm, and maximal abduction angle was increased in 5.8degrees. CONCLUSION: Incomplete syndactyly near proximal interphalangeal joint was corrected by modified seven flap plasty and was able to get a satisfactory result.

Toe Tissue Transfer for Reconstruction of Damaged Digits due to Electrical Burns

BACKGROUND: Electrical burns are one of the most devastating types of injuries, and can be characterized by the conduction of electric current through the deeper soft tissue such as vessels, nerves, muscles, and bones. For that reason, the extent of an electric burn is very frequently underestimated on initial impression. METHODS: From July 1999 to June 2006, we performed 15 cases of toe tissue transfer for the reconstruction of finger defects caused by electrical burns. We performed preoperative range of motion exercise, early excision, and coverage of the digital defect with toe tissue transfer. RESULTS: We obtained satisfactory results in both functional and aesthetic aspects in all 15 cases without specific complications. Static two-point discrimination results in the transferred toe cases ranged from 8 to 11 mm, with an average of 9.5 mm. The mean range of motion of the transferred toe was 20degrees to 36degrees in the distal interphalangeal joint, 16degrees to 45degrees in the proximal interphalangeal joint, and 15degrees to 35degrees in the metacarpophalangeal joint. All of the patients were relatively satisfied with the function and appearance of their new digits. CONCLUSIONS: The strategic management of electrical injury to the hands can be both challenging and complex. Because the optimal surgical method is free tissue transfer, maintenance of vascular integrity among various physiological changes works as a determining factor for the postoperative outcome following the reconstruction.

A Clinical Experience of Total Scalp Avulsion in a Male

Total scalp avulsion is rare but a devastating injury. This condition burdens the patient with disfigured cosmetic appearance and permanent psychosocial trauma. Throughout history, this condition has been favored in women working with mechanics since the long hair function as a vector appliance for oblique pull of the hair into a stationary torque. We present our experience of the replantation of the total avulsed scalp in male, first to be reported in Korea. Warm ischemic time was exceeding 16 hours along with severe crushed condition of the detached margin, a relatively satisfactory result was obtained.

Clinical experience in the treatment of piriformis syndrome using pulsed radiofrequency: A case report

Piriformis syndrome consists of pain, tingling sensation, and paresthesia in areas innervated by sciatic nerve and is one of the main causes of low back pain. A 43-year-old male made a visit for continuous left buttock pain and tingling sensation in lower limbs for three years. Medication, epidural block and sacroiliac joint block were performed, but without effect. Sciatic nerve block with local anesthetics and steroid, however, showed some improvement for a short period of time. The patient's symptoms, physical examination, and the fact that sciatic nerve block showed improvement for a while led to the suspicion of piriformis syndrome. Thus, pulsed radiofrequency was performed on sciatic nerve twice. Visual analog scale (VAS) was 8-9 on first visit, which decreased to 1 after treatment and lasted for more than 18 months.

Multiple Epidermal Inclusion Cysts in Previous Bone Graft Site of the Thumb: A Case Report

We report a 71-year-old male presenting with painful growing mass on his left thumb. The patient had received iliac bone graft on his left thumb 20 years ago, and removed all the grafted bone 8 years ago due to recurrent ulcer. Biopsy revealed multiple eidermal inclusion cysts on the dorsal surface of the bone graft site. Surgeon should be aware of epidermal inclusion cyst occurred at the previous bone graft site of the finger.

Comparison of the BACTEC Blood Culture and Conventional Culture Methods for Isolation of Microorganisms Causing Peritonitis in CAPD Patients / 대한내과학회지

BACKGROUND/AIMS: Peritonitis is the most frequent complication of continuous ambulatory peritoneal dialysis (CAPD). Prompt recognition and treatment of peritonitis is important. The purpose of this study was to compare the effectiveness of isolation of the microorganisms causing CAPD peritonitis by the BACTEC blood culture and conventional methods. METHODS: We retrospectively reviewed 38 episodes of peritonitis in 34 CAPD patients between September 2007 and February 2010. Two methods of processing dialysate from patients on CAPD were used. Blood culture was performed using two 10-mL effluents, which were inoculated into a pair of BACTEC culture bottles. The conventional method was performed using 50 mL of centrifuged dialysate. The sedimented dialysate was inoculated onto blood agar and MacConkey agar plates or into thioglycollate broth. To evaluate effectiveness, we compared the rate of positive culture results and the time to identify the causative organism of the two culture methods. RESULTS: Use of the BACTEC bottle method resulted in more positive culture results than did conventional culture (86.8 vs. 57.9% p = 0.003). The time taken to identify the causative organism from culture-positive peritonitis was more rapid using the blood culture compared with the conventional culture method (90 vs. 109 hr, p = 0.03). CONCLUSIONS: Blood culture using the BACTEC bottle is more effective than the conventional culture technique for detection of causative microorganisms in CAPD peritonitis.

The Comparison between 6th and 7th International Union Against Cancer/American Joint Committee on Cancer Classification for Survival Prognosis of Gastric Cancer / 대한소화기학회지

BACKGROUND/AIMS: The tumor-node-metastasis (TNM) staging is an useful system to assess the prognosis of any solid cancer. As new TNM staging classification of 7th stomach cancer was revised in 2009, we evaluated the prognostic predictability of the 7th International Union Against Cancer/American Joint Committee on Cancer (UICC/AJCC) TNM classification compared to 6th UICC/AJCC TNM classification in gastric cancer. METHODS: From January 2000 to December 2009, 5-year survival rates of 266 patients with gastric cancer were calculated by the 6th and 7th UICC/AJCC TNM classification. RESULTS: Using the 7th UICC/AJCC TNM classification, there was no significant difference in the 5-year cumulative survival rates (5 YSR) between stage IIA and IIB, IIB and IIIA, and IIIA and IIIB (70% vs. 71%, p=0.530; 71% vs. 80%, p=0.703; 80% vs. 75%, p=0.576, respectively) though significant differences of the survival rates were observed among stages of 6th edition. Using T stage of 7th edition, 5 YSR was not different between T2 and T3 (86% vs. 82%, p=0.655). Using N stage of 7th edition, 5 YSR were not different between N1 and N2, N3a and N3b (79% vs. 81%, p=0.506; 41% vs. 17%, p=0.895, respectively). CONCLUSIONS: The 7th UICC/AJCC TNM classification had poor prognostic predictability in gastric cancer compared to the 6th edition.

Augmentation Genioplasty Using the Multiporous High Density Polyethylene(Medpor(R))

Microgenia is that the mental protuberance is small state because of symphysis did not developed properly while occlusion and size of mandible are normal. One or two-step sliding advancement genioplasty is mainly performed to make good aesthetic harmony with face, but in slight or moderate degree of microgenia patients who do not want general anesthesia or osteotomy, the multiporous high-density polyethylene(Medpor(R)) can be used. It is easy to carve and bend, and has a variety of size and shape to fit the contour of the chin anatomy. Under the local anesthesia. a vertical incision which can preserve mentalis muscle is made about 2 cm at inferior labial sulcus along inferior frenulum in the jaw midline. Subperiosteal dissection is performed to make a pocket. Seperated Medpor(R)s are inserted in each side and reassembled into one in the midline. To minimize bone erosion, implant has to be placed on the inferior side of mandible edge and fixed with screw. Bandage compression was applied for 3 days and antibiotics was treated for 7 days postoperatively. This technique has a small incision, easy procedure and faster recovery. During the follow-up period, there were no specific complications and patients were all satisfied to their result.

Myositis Ossificans on the Nasal Dorsum: A Case Report

PURPOSE: Myositis ossificans is a benign condition of heterotopic bone formation that still requires more of its pathologic explanation. The lesions are localized predominantly to the high-risk sites of injury, involving flexor muscles of the upper limbs and thigh, but rarely in the head and neck area. METHODS: A case of a 44-year-old male patient presented with a palpable hard mass on nasal dorsum. The patient experienced a similar lesion on upper limb few years ago. On computed tomographic image, the lesion presented focal definite increase in opacity compatible to adjacent bone densitiy on nasal dorsum. RESULTS: The lesion was excised under open rhinoplasty incision. The pathologic report revealed focal bone formation and calcification within skeletal muscle. CONCLUSION: We describe a unique and only case of a myositis ossificans on nasal dorsum which is indifferent from previous concept.