Alagille syndrome (AGS) is a rare autosomal dominant inherited disorder, with major clinical manifestations of bile duct paucity, cholestasis, cardiovascular anomaly, ophthalmic abnormalities, butterfly vertebrae, and dysmorphic facial appearance. It is caused by heterozygous mutations in JAG1 or NOTCH of the Notch signaling pathway presenting with variable phenotypic penetrance and involving multiple organ systems. The following case report describes a unique case of a 16-year-old female with AGS who presented with the primary complaint of renovascular hypertension. She had a medical history of ventricular septal defect and polycystic ovary syndrome. The patient had a dysmorphic facial appearance including frontal bossing, bulbous tip of the nose, a pointed chin with prognathism, and deeply set eyes with mild hypertelorism. Stenoocclusive changes of both renal arteries, celiac artery, lower part of the abdominal aorta, and left intracranial artery, along with absence of the left internal carotid artery were found on examination. Whole exome sequencing was performed and revealed a pathologic mutation of JAG1, leading to the diagnosis of AGS. Reverse phenotyping detected butterfly vertebrae and normal structure and function of the liver and gallbladder. While the representative symptom of AGS in most scenarios is a hepatic problem, in this case, the presenting clinical features were the vascular anomalies. Clinical manifestations of AGS are diverse, and this case demonstrates that renovascular hypertension might be in some cases a presenting symptom of AGS.

Purpose: The introduction of immune checkpoint inhibitors represents a major advance in the treatment of lung cancer, allowing sustained recovery in a significant proportion of patients. Nivolumab is a monoclonal anti–programmed death cell protein 1 antibody licensed for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) after prior chemotherapy. In this study, we describe the demographic and clinical outcomes of patients with advanced NSCLC treated with nivolumab in the Korean expanded access program. Materials and Methods: Previously treated patients with advanced non-squamous and squamous NSCLC patients received nivolumab at 3 mg/kg every 2 weeks up to 36 months. Efficacy data including investigator-assessed tumor response, progression data, survival, and safety data were collected. Results: Two hundred ninety-nine patients were treated across 36 Korean centers. The objective response rate and disease control rate were 18% and 49%, respectively; the median progression-free survival was 2.1 months (95% confidence interval [CI], 1.87 to 3.45), and the overall survival (OS) was 13.2 months (95% CI, 10.6 to 18.9). Patients with smoking history and patients who experienced immune-related adverse events showed a prolonged OS. Cox regression analysis identified smoking history, presence of immune-related adverse events as positive factors associated with OS, while liver metastasis was a negative factor associated with OS. The safety profile was generally comparable to previously reported data. Conclusion This real-world analysis supports the use of nivolumab for pretreated NSCLC patients, including those with an older age.

Broussonetia kazinoki Siebold. (B. kazinoki) has long been used in the manufacture of paper in Asian countries. Although B. kazinoki leaves (BK) have been employed in dermatological therapy, use of BK has not been tested in patients with atopic dermatitis (AD). Using Nc/Nga mice, which are genetically predisposed to develop AD-like skin lesions, we confirmed the efficacy of BK in AD treatment. BK extract was applied topically to Dermatophagoides farinae-induced AD-like lesions in Nc/Nga mice, and the effects were assessed both clinically and by measuring skin thickness on the back and ears. We measured the effects of BK extract on plasma levels of IgE and IL-4. We also measured the ability of BK extract to inhibit the secretion of hTARC in HaCaT cells after stimulation by TNF-alpha and IFN-gamma. We found that BK extract significantly reduced ear and dorsal skin thickness and the clinical signs of AD, as well as significantly down-regulating the plasma levels of IgE and IL-4 (p<0.01 for each comparison). Moreover, 500 mug/mL of BK extract inhibited hTARC secretion in HaCaT cells by activated TNF-alpha/IFN-gamma by about 87%. These findings suggest that topical application of BK extract has excellent potential in the treatment of AD.
Animals ; Asian Continental Ancestry Group ; Broussonetia* ; Dermatitis, Atopic ; Ear ; Humans ; Immunoglobulin E ; Interleukin-4 ; Mice* ; Mites* ; Plasma ; Pyroglyphidae ; Skin ; Tumor Necrosis Factor-alpha

BACKGROUND AND OBJECTIVES: Neural cell adhesion molecule (NCAM) and polysialic acid (PSA) function basically in cell adhesion and migration. In neural development, they are closely associated with axon pathfinding, synaptogenesis, neural cell migration, differentiation and myelination. The purpose of this study is to assess expression of NCAM and PSA expression in spiral ganglion neurons and Schwann cells and to postulate their functions. MATERIALS AND METHOD: Guinea pig spiral ganglion cells were harvested and cultured in vitro. The cells were grown and differentiated in culture medium together with brain derived neurotrophic factor (BDNF), neurotrophin 3 (NT-3) and glial cell derived neurotrophic factor (GDNF). After 1 week of culturing, the cells were fixed and immunocytochemical staining with beta-III tubulin, S-100, polysialic acid (PSA) and neural cell adhesion molecule (NCAM) were performed. We then checked axon growth rate with Axon Analyzer System(R). RESULTS: In the spiral ganglion culture, cultured neurons showed positive staining for beta-III tubulin, NCAM, and different expressions of PSA. S-100 positive glial cells (Schwann cells) showed different expressions of NCAM and no expression of PSA. Some NCAM positive neurons and Schwann cells were in contact each other. The growth rate of neuron was about 10-30 micrometer/h using Axon Analyzer System(R). CONCLUSION: We postulated that NCAM may play an important role in neural cell adhesion, myelination, fasciculation and ganglion formation. But PSA did not express the adhesive function of NCAM ; its absence may have been due to developmental reason. The differential expression of NCAM in the Schwann cells may indicate its different immunocytochemical characteristics and functions as shown in the CNS glial cells, astrocytes and oligodendrocytes.
Adhesives ; Animals ; Astrocytes ; Axons ; Brain-Derived Neurotrophic Factor ; Cell Adhesion ; Cell Movement ; Fasciculation ; Ganglion Cysts ; Guinea Pigs ; Myelin Sheath ; Neural Cell Adhesion Molecules* ; Neuroglia ; Neurons* ; Neurotrophin 3 ; Oligodendroglia ; Schwann Cells ; Spiral Ganglion* ; Tubulin

PURPOSE: Effective hemodialysis for a patient with end-stage renal disease (ERDS) is dependent upon a durable, low-morbidity vascular access. Although It is generally agreed that the distal radiocephalic fistula originally discribed by Brescia and Cimino is the most effective primary access constrruction, no consensus exists regarding primary and secondary alternatives for patients with inadequate of failed rediocephalic prodedures. Many options are available, but the relative value of these alternative operations is unclear. Therefore the place of the basilic vein in secondary acccess construction needs to be assessed. We evaluated if the basilic vein can be used to construct a durable, low-morbidity access. METHODS: A native brachio-basilic arterio-venous fistula with superficial transposition has been performed, for lack of usuable vein on 54 forearm in 47 patients from August 1995 to October 1999 (Male: 15, female: 32) with mean age 51 years (26 to 70 years). RESULTS: The main cause of renal insufficiency were: diabetes 27 (57.4%), hypertensive 19 (40.4%), renal tuberculosis 2 (4.3%) and renal cyst 1 (2.1%). The waiting period before vascular access puncture has been 28 6 days. Eight (17.0%) stenosis has been detected and, forearm and/or hand edema occured in three (6.4%); thrombosis in two (4.3%); bleeding in two (4.3%); pseudoaneurysm in one. Through the follow-up periods of 50 months, the primary patency was 80.9% at 12 months and 78.7% at 24 months. CONCLUSION: The brachio-basilic fistula with superficial transposition of basilic vein is a valuable vascular access for diabetes, female old patients, and can remain an alternative method for even younger patients by avoiding the installation of artificial graft after failed forearm arteriovenous fistula.
Aneurysm, False ; Arteriovenous Fistula* ; Consensus ; Constriction, Pathologic ; Edema ; Female ; Fistula ; Follow-Up Studies ; Forearm ; Hand ; Hemorrhage ; Humans ; Kidney Failure, Chronic ; Ocimum basilicum* ; Punctures ; Renal Dialysis* ; Renal Insufficiency ; Thrombosis ; Transplants ; Tuberculosis, Renal ; Veins*

BACKGROUND: An important metabolic feature of acromegaly is a reduced action of insulin on hepatic gluconeogenesis and peripheral glucose disposal which mediated by growth hormone hypersecretion. Octreotide, a synthetic octapeptide somatostatin analogue exerts complex effects on hormonal and metabolic regulations affecting glucose homeostasis. This study was designed to ascertain the shorterm effect of octreotide on glucose tolerance in acromegaly. METHODS: 10 patients (five men and five women, age 47.9+/-11.8) were injected subcutaneously with octreotide, 100 micrograms for 24 hours. Patients were assessed with respect to growth hormone, glucose, and insulin response to a standard 100 g oral glucose tolerance test (OGTT) before and during the last 2 hour of octreotide infusion. RESULTS: During the therapy, there was significant decrease in mean blood glucose response to OGTT (678.4+/-51.9 vs 581.9+/-47.3 mg/dL/2hr: mean areas under the glucose curve, p=0.01) and mean serum insulin response to oral glucose load was significantly reduced in all patients (339.2+/-106.2 vs 256.7+/-111.3 U/mL/2hr: mean areas under the insulin curve, p=0.01). Using glucose tolerance test criteria three patients of 10 had normal glucose tolerance, four and three had impaired glucose tolerance and diabetes, respectively, at base line. While on octreotide these composition was changed to six patients of NGT, three of IGT and one diabetes. CONCLUSION: We conclude that insulin resistance mediated by GH hypersecretion was improved by shorterm octreotide treatment.
Acromegaly* ; Blood Glucose ; Female ; Gluconeogenesis ; Glucose Tolerance Test ; Glucose* ; Growth Hormone ; Homeostasis ; Humans ; Infusions, Subcutaneous* ; Insulin ; Insulin Resistance ; Male ; Octreotide* ; Social Control, Formal ; Somatostatin

BACKGROUND AND OBJECTIVE: Eosinophil is a major inflammatory cell in allergic diseases and parasitic infestations. Various cytokines such as GM-CSF, IL-3 and IL-5 are known to activate eosinophils and prolong their survival. Among them, IL-5 is the most potent stimulator of eosinophil survival. Recently, it was reported that increased expression of Bcl-2 is related to prolonged survival of IL-5 stimulated eosinophil. Theophylline is a useful drug in bronchial asthma, due not only to bronchial dilation but also to its anti-inflammatory effects. It has been suggested that anti inflammatory action of theophylline derives from the reduction of inflammatory cells in the airways which is mechated by stimulat on of apoptosis of inflammatory cells. In this study, we investigated, by measuring Bcl-2 expression of IL-5 stimulated eosinophil, the effect of theophylline on apoptosis as one of the anti-inflammatory action. MATERIAL AND METHOD: Peripheral eosinophils were isolated from atopic patients by using Perco- 11 discontinuous gradient and purified by negative selection technique using MACS. Eosinophil viability and apoptosis were measured by FACscan. Expression of Bcl-2 protein in eosinophils was detected by Western blot and ELISA. RESULTS: IL-5 increased the percentage of viable eosinophils and reduced the apoptosis of eosinophils in a dose dependent manner. The increased survival of IL-5 stimulated eosinophils was reduced by theophylline via activation of apoptosis. Bcl-2 was increased when eosinophils were cultured with IL-5 only, but when theophylline was cocultured, reduced Bcl-2 was seen with Western blot and ELISA. CONCLUSION: IL-5 increases the survival of eosinophil through the enhanced expression of Bcl- 2. Theophylline has counter action against IL-5 via inhibition of Bcl-2 induced by IL-5. Inhibiting the prolongation of eosinophil survival caused by IL-5 might be one possible mechanism of antiinflammatory effects of theophylline.
Apoptosis ; Asthma ; Blotting, Western ; Cytokines ; Enzyme-Linked Immunosorbent Assay ; Eosinophils* ; Granulocyte-Macrophage Colony-Stimulating Factor ; Humans ; Interleukin-3 ; Interleukin-5 ; Theophylline*

OBJECTIVES: The poor survival rates among patients receiving surgery alone for stages II and III non-small cell lung cancer prompted several trials of adjuvant therapy after resection. We performed a prospective phase II study in patients with stage II-IIIA non-small cell lung cancer after resection to evaluate the feasibility, activity and toxicity of the postoperative sequential MVP chemotherapy and radiotherapy. METHODS: Between February 1991 and May 1995, 60 patients with resected stage II, IIIA non-small cell lung cancer received 2 cycles of MVP combination chemotherapy (Mitomycin-C 6 mg/m2, Vinblastine 6 mg/m2, Cisplatin 60 mg/m2) within 3 weeks after surgery, followed by thoracic irradiation (5,040 cGy after complete resection and 900 cGy booster to microscopically positive resection margin at 1.8 Gy per fraction) within 3-4 weeks after chemotherapy. RESULTS: Forty nine men and 11 women with a median age of 60.5 years (range 33-81 years) were included. During the median follow-up period of 828 days (61-2,015 days), 25 patients had developed recurrence. Among the 25 failures, 3 were local relapse only and 20 were distant metastasis only and 2 had both local and distant sites of recurrence. Three-year overall survival and event-free survival were 43% and 37%, respectively. Neutropenia of grade I-II was observed only in 13 patients. Eleven patient showed grade I-II radiation pneumonitis and 32 had grade I-II radiation esophagitis. CONCLUSION: Postoperative sequential MVP chemotherapy and radiotherapy in resected stage II-IIIA non-small cell lung cancer is well-tolerated and shows interesting activity.
Carcinoma, Non-Small-Cell Lung* ; Cisplatin* ; Disease-Free Survival ; Drug Therapy* ; Drug Therapy, Combination ; Esophagitis ; Female ; Follow-Up Studies ; Humans ; Male ; Mitomycin* ; Neoplasm Metastasis ; Neutropenia ; Prospective Studies ; Radiation Pneumonitis ; Radiotherapy* ; Recurrence ; Survival Rate ; Vinblastine*

BACKGROUND: There is difference between isoflurane and enflurane in the myocardial sensitization to catecholamines, and their actions on the heart. Enflurane reduces cytoplasmic calcium more than isoflurane. The hypothesis could be suggested that these two volatile anesthetics might cause the different incidences and natures of cardiac arrhythmias. METHODS: The anesthesia was induced by the intravenous injection of thiopental(6 mg, kg-1) and pipecuronium(0.1 mg, kg-1). Two groups were randomly allocated to the patients(n=80) in the maintenance: Group I inhaled isoflurane(1~2%), O2(2 L), and N2O(2 L), Group II, enflurane (1.5~2.5%). Continuous electrocardiographic recordings with Holter monitor were made of those undergoing tympanoplasty during anesthesia. The tapes recorded were scanned using analyzer, and we read out ECG complexes on the screen. Results were categorized as induction, maintenance, and emergence, and inferred from unpaired t-test, and X2-test with p<0.05 considered significant. RESULTS: The results were as follows: 1) The total incidence of cardiac arrhythmias was 65.0%. Isoflurane(52.5%) was lower than enflurane(77.5%) in the incidence. 2) During maintenance and emergence, isoflurane was lower than enflurane in the frequency of supraventicular arrhythmias. 3) Ventricular arrhythmias most frequently occurred in induction. 4) The frequency of supraventricular arrhythmias was more than two times that of ventricular ones. The arrhythmias at the AV junction were the most common, and VPC's the second. CONCLUSIONS: Greatest caution should be paid during peri-induction. It could be suggested that compared to enflurane, isoflurane better be administered for those to whom arrhythmias could be harmful.
Anesthesia ; Anesthetics ; Arrhythmias, Cardiac* ; Calcium ; Catecholamines ; Cytoplasm ; Electrocardiography ; Enflurane* ; Heart ; Incidence* ; Injections, Intravenous ; Isoflurane* ; Tympanoplasty

Primary mediastinal nonseminomatous germ cell tumor is extremely rare. Apart from rarity and large size, mediastinal germ cell tumors show striking similarity to testicular tumors in age, incidence, and tumor type. The symptoms associated with these tumors are related mainly to size, invasion of neighboring structures, and distant metastases. Tissue diagnosis is obtained by biopsy of the primary lesion or by biopsy of metastatic sites. Tumors often present with advanced bulky disease, which are unresectable. So these tumors require an aggressive multidisciplinary approach to management. Optimal management includes aggressive surgical debulking and early use of cisplatin-bleomycin-based combination chemotherapy. Serial biomarker measurements permit early recognition of recurrence and improved timing of surgical intervention. The prognosis for mediastinal germ cell tumors is poor, not only because they are far advanced at the time of diagnosis but also because some of the tumors-such as embryonal carcinomas, choriocarcinomas, and endodermal sinus tumors-are very aggressive. In these cases, we present three young male patients with large mass on anterior mediastinum. Tissue diagnosis was obtained by primary lesion biopsy. All patients received surgical debulking and combination chemotherapy and experienced a brief response and eventually had relapses. We report these cases with a review of literatures.
Biopsy ; Carcinoma, Embryonal ; Choriocarcinoma ; Diagnosis ; Drug Therapy, Combination ; Endoderm ; Endodermal Sinus Tumor ; Female ; Germ Cells* ; Humans ; Incidence ; Male ; Mediastinum ; Neoplasm Metastasis ; Neoplasms, Germ Cell and Embryonal* ; Pregnancy ; Prognosis ; Recurrence ; Strikes, Employee ; Testicular Neoplasms