Vulvar squamous cell carcinoma (SCC) consists of two different etiologic categories: human papilloma virus (HPV)-associated (HPV (+)) and HPV-non-associated (HPV (−)). There have been no genome-wide studies on the genetic alterations of vulvar SCCs or on the differences between HPV (+) and HPV (−) vulvar SCCs. In this study, we performed whole-exome sequencing and copy number profiling of 6 HPV (+) and 9 HPV (−) vulvar SCCs and found known mutations (TP53, CDKN2A and HRAS) and copy number alterations (CNAs) (7p and 8q gains and 2q loss) in HPV (−) SCCs. In HPV (+), we found novel mutations in PIK3CA, BRCA2 and FBXW7 that had not been reported in vulvar SCCs. HPV (−) SCCs exhibited more mutational loads (numbers of nonsilent mutations and driver mutations) than HPV (+) SCCs, but the CNA loads and mutation signatures between HPV (+) and HPV (−) SCCs did not differ. Of note, 40% and 40% of the 15 vulvar SCCs harbored PIK3CA and FAT1 alterations, respectively. In addition, we found that the SCCs harbored kataegis (a localized hypermutation) in 2 HPV (+) SCCs and copy-neutral losses of heterozygosity in 4 (one HPV (+) and 3 HPV (−)) SCCs. Our data indicate that HPV (+) and HPV (−) vulvar SCCs may have different mutation and CNA profiles but that there are genomic features common to SCCs. Our data provide useful information for both HPV (+) and HPV (−) vulvar SCCs and may aid in the development of clinical treatment strategies.

BACKGROUND/AIMS: Immunoglobulin A nephropathy (IgAN) is a generally progressive disease, even in patients with favorable prognostic features. In this study, we aimed to investigate the antiproteinuric effect and tolerability of low-dose valsartan (an angiotensin II receptor blocker) therapy in normotensive IgAN patients with minimal proteinuria of less than 0.5 to 1.0 g/day. METHODS: Normotensive IgAN patients, who had persistent proteinuria with a spot urine protein-to-creatinine ratio of 0.3 to 1.0 mg/mg creatinine, were recruited from five hospitals and randomly assigned to either 40 mg of valsartan as the low-dose group or 80 mg of valsartan as the regular-dose group. Clinical and laboratory data were collected at baseline, and at 4, 8, 12, and 24 weeks after valsartan therapy. RESULTS: Forty-three patients (low-dose group, n = 23; regular-dose group, n = 20) were enrolled in the study. Proteinuria decreased significantly not only in the regular-dose group but also in the low-dose group. The change in urine protein-to-creatinine ratio at week 24 was -41.3% +/- 26.1% (p < 0.001) in the regular-dose group and -21.1% +/- 45.1% (p = 0.005) in the low-dose group. In the low-dose group, blood pressure was constant throughout the study period, and there was no symptomatic hypotension. In the regular-dose group, blood pressure decreased at weeks 8 and 12. No significant change in glomerular filtration rate, serum creatinine level, or serum potassium level was observed during the study period. CONCLUSIONS: Our results suggest that low-dose valsartan can significantly reduce proteinuria without causing any intolerability in normotensive IgAN patients with minimal proteinuria.
Adult ; Angiotensin II Type 1 Receptor Blockers/*administration & dosage/adverse effects ; Biomarkers/urine ; Blood Pressure ; Creatinine/urine ; Female ; Glomerulonephritis, IGA/diagnosis/*drug therapy/physiopathology/urine ; Humans ; Male ; Middle Aged ; Prospective Studies ; Proteinuria/diagnosis/*drug therapy/physiopathology/urine ; Republic of Korea ; Time Factors ; Treatment Outcome ; Valsartan/*administration & dosage/adverse effects

Inflammatory bowel disease often involves extra-intestinal organs. Cerebral thrombosis, portal vein thrombosis and pulmonary thrombosis have been reported. Deep vein thrombosis and pulmonary thromboembolism are significant causes of mortality in patients with inflammatory bowel disease. A 48-year-old woman was diagnosed as inflammatory bowel disease on colonoscopy and histology. We used hydrocortisone and mesalazine for the treatment of disease. Nineteen days later, she complained of abrupt dyspnea. Pulmonary CT angiography revealed a thromboembolism in right pulmonary arteries. After the treatment of heparin therapy, follow-up pulmonary CT angiography showed significant improvement of previously thrombosed pulmonary arteries.
Acute Disease ; Colitis, Ulcerative/complications/*diagnosis ; Colonoscopy ; Female ; Humans ; Middle Aged ; Pulmonary Embolism/*diagnosis/etiology/pathology ; Tomography, X-Ray Computed

OBJECTIVE: The purpose of this study was to determine whether unexplained elevation of second-trimester maternal serum beta-human chorionic gonadotropin (beta-hCG) is associated with adverse pregnancy outcomes. METHOD: Between January 1998 and December 1999, we evaluated 2112 pregnant women undergoing second trimester triple marker screening test who delivered at our hospital. Inclusion criteria were singleton pregnancy, confirmed gestational age, and hCG level greater than 2.0 MoM. The exclusion criteria were fetal anomaly, abnormal karyotype, MSAFP level greater than 2.0 MoM, uE3 level less than 0.4 MoM, and referred patients with pregnancy-induced hypertension (PIH). A group of randomly selected women with normal maternal serum hCG and AFP levels served as control. RESULTS: Women with unexplained elevation of hCG level showed increased risks for PIH (p<0.001) and preterm delivery (p<0.003). There were no significant diffrences between study and control groups with respect to placental abruption, fetal distress, PROM, intrauterine fetal death, and apgar score. CONCLUSION: Pregnancies with unexplained elevation of hCG levels should be regarded as high-risk pregnancies and managed accordingly. The combination with these biomarkers such as VEGF, plasminogen activating factor I and AT-III as a screening test for PIH may be useful.
Abnormal Karyotype ; Abruptio Placentae ; Apgar Score ; Biomarkers ; Chorionic Gonadotropin ; Female ; Fetal Death ; Fetal Distress ; Fibrinogen ; Gestational Age ; Humans ; Hypertension, Pregnancy-Induced ; Mass Screening ; Plasminogen ; Pregnancy ; Pregnancy Outcome* ; Pregnancy Trimester, Second* ; Pregnancy* ; Pregnancy, High-Risk ; Pregnant Women ; Vascular Endothelial Growth Factor A

Calcitriol therapy is an important treatment for the prevention and control of secondary hyperparathyroidism in continuous ambulatory peritoneal dialysis (CAPD) patients. However, this often has been limited by the associated hypercalcemia and hyperphosphatemia due to increase in intestinal calcium and phosphorus absorption. Many studies reported that these limitations could be avoided by changing routes, frequency and dose of calcitriol treatment. But, there are still controversy about each methods and the results on the PTH response to conventional calcitriol treatment in CAPD patients. This study was performed to evaluate the factors affecting the response to oral calcitriol in CAPD patients. A retrospective study was done in 92 CAPD patients with secondary hyperparathyroidism(intact PTH level >200pg/ml) on oral calcitriol treatment. After baseline study of serum calcium, phosphorus, alkaline phosphatase, BUN, creatinine and intact PTH, calcitriol therapy was begun via oral rou- te, daily. Serum calcium, phosphorus, alkaline phosphatase, BUN, creatinine, intact FI'H and other bio- chemical markers were checked at 3 month, 6 month after treatment. Parathyroid gland ultrasonography was performed to detect parathyroid hypertrophy and nodule and to measure the diameter of parathymid gland. All the patients were divided into two groups according to percent reduetion of i-PTH(initial PTH PTH after 3, 6 months)X100/initial PTH(%),deltaPTH during oral calcitriol therapy for 3 and 6 months(group I ; delta PTH >30%, group II ; delta PTH <30%). RESULT: 1) All 92 patients(mean age 46.5 11.3yr, M: F 45: 47, mean CAPD duration 51.3 39.4 months) were administered oral calcitriol, daily. Mean calcitriol dose during 3 month was 0.43 0.22Mg and during 6month 0.43 0.24Mg. 2) After 3-month treament, there were significant differences in initial i-PTH, the diameter of parathyroid gland, initial phosphorus, intial total alkaline phosphatase and duration of CAPD between group I and II(406.7+/-196.5 vs. 871.0+/-478Apglml, 6.2+/-2.6 vs. 13.1+/-5.2mm, 5.0+/-1.3 vs. 5.7+/-1.3mg/dl, 93.7+/-4L1 vs. 171.9+/-137.6IU/L, 40.1+/-34.9 vs. 73.5+/-37.8months, p< 0.05, respectively). 4) After 6-month treament, there were significant differences in initial i-PTH, the diameter of parathyroid gland, intial total alkaline phosphatase and duration of CAPD between group I and II(474.1+/-266.6 vs. 889.7+/-485.4pg/ml, 6.4+/-2.7 vs. 14.5+/-5.1mm, 107.9+/-80.1 vs. 180.7+/-121.5IU/L, 40.5+/- 32.9 vs. 81.8+/-35.3months, p<0.05, respectively). 5) The significant negative correlation was shown between deltaPTH and the duration of peritoneal dialysis, the diameter of parathyroid gland, initial PTH level and PTH response during 3-month and 6-month oral calcitriol treatment. The response to oral calcitriol was poor when i-PTH level more than 500pg/ml(kappa 0.429, p value <0.01), the diameter of parathyroid gland more than 10.0mm(kappa 0.641, p value<0.01), the duration of CAPD more than 55months(kappa 0.524, p value< 0.01). These data suggested that initial i-PTH level, the diameter of parathyroid gland size and the duration of CAPD were independent risk factors of the poor response to oral calcitriol therapy in CAPD patients with secondary hyperparathyroidism.
Absorption ; Alkaline Phosphatase ; Calcitriol* ; Calcium ; Creatinine ; Humans ; Hypercalcemia ; Hyperparathyroidism, Secondary* ; Hyperphosphatemia ; Hypertrophy ; Parathyroid Glands ; Peritoneal Dialysis ; Peritoneal Dialysis, Continuous Ambulatory* ; Phosphorus ; Retrospective Studies ; Risk Factors ; Ultrasonography

It's well known that protein/creatinine ratio(P/C ratio) in random urine samples reflects 24-hour urine protein. However, the factors affecting accurate quantitation of proteinuria using random urine P/C ratio are not fully evaluated. The aim of this study is to evaluate factors affecting accurate quantitaion of proteinuria using random urine P/C ratio. 118 patients admitted in Yonsei university medical center during June 1998 and Dec. 1998 were assessed for the measurement of random urine protein/creatinine ratio from second voided urine. 118 patients(mean age 41.5year, male: female 2.36: 1) had mean creati-nine level 1.83+/-1.78mg/dL, 24-hour pmteinuria 6.06+/-7.64g/day and P/C ratio 4.80+/-4.48, All the patiient.s were divided into A, B, C, I, II, K, IV according to serum creatinine level and 24-hour proteinurim amount. The correlation coefficient(R value) between proteinuria and P/C ratio are shown that in all pa- tients is 0.875, group A(Cr* Academic Medical Centers ; Creatinine ; Female ; Humans ; Male ; Proteinuria* ; Sensitivity and Specificity

The most widely used method for treatment of secondary hyperparathyroidism(SH) in CAPD patients has been the administration of calcitriol by oral route. In this study, we compared the efficacy and safety of daily low dose calcitriol therapy with those of intermittent high dose pulse therapy. The study group consisted of 38 patients undergoing CAPD with serum intact PTH level of more than 200pg/ mL. Twenty patients were randomly administered daily low dose calcitriol(0.25 microgram/day for 1 month followed by 0.5 microgram daily dose for the next 3 mon-ths) while 18 patients were given intermittent pulse therapy (0.5 microgram-0.5 microgram-0.75 microgram 3 times a week for 1 month, increased to 1.0 microgram-1.25 microgram-1.25 microgram 3 times a week for the next 3 months). Thirty five patients completed the study : 17 on daily oral calcitriol (M: F=0.7:1, mean age=47.3+/-10.6 years, mean duration of CAPD=48.9+/-41.1 months), and 18 on oral pulse calcitriol (M:F=1.6:1, mean age=41.5+/-12.7 years, mean duration of CAPD=49.2+/-41.6 months). The baseline serum levels of calcium, phosphorus, i-PTH, alkaline phosphatase, and total CO2 were not different between daily and pulse group(9.5+/-0.8 vs 9.3+/-0.9mg/dL, 5.8+/-1.3 vs 5.1+/-1.2mg/dL, 443.1+/-162.5 vs 546+/-385.9pg/mL, 91.8+/-47.7 vs 108.9+/-66.5IU/L, 23.7+/-1.9 vs 25.5+/-2.0mEq/L, p>0.05, respectively). The i-PTH level decreased significantly in daily calcitriol group after 1 month (332.8+/-214.8pg/mL, p<0.01), and at final evaluation (180.4+/-254.8pg/mL, p<0.01). In pulse calcitriol group, i-PTH level also decreased significantly to 400,4+/-225.8pg/mL(p<0.05), 89.4+/-122.6 pg/mL(p<0.01), respectively. The rate of decline in i-PTH level from baseline were similar(daily=25.4+/-22.7 vs pulse=19.5+/-12.6%decline/month, p>0.05). The serum calcium increased similarly in both groups after treatment (daily=10.6+/-0.8 vs pulse=l0.1+/-1.0mg/dL, p>0.05). Hypercalcemia(>11.0mg/dL) was rarely observed in all patients (daily=5, pulse=8 episodes). In conclusion, both daily and pulse calcitriol therapy were similarly effective and safe in control of SH.
Alkaline Phosphatase ; Calcitriol* ; Calcium ; Humans ; Hyperparathyroidism, Secondary* ; Peritoneal Dialysis* ; Peritoneal Dialysis, Continuous Ambulatory ; Phosphorus

No abstract available.
Neoplasm Metastasis* ; Skull* ; Thyroid Gland* ; Thyroid Neoplasms*

Renal artery stenosis may be a cause of hypertension and a potential contributor to progressive renal insufficiency. However, the prevalence of renal artery disease in a general population is poorly defined. The purposes of this study were to evaluate the prevalence of angiographically-determined renal artery narrowing in a patient population undergoing routine cardiac catheterization, and to identify the risk factors for renal artery stenosis. After left ventriculography, abdominal aortography was performed to screen for the presence of renal artery stenosis. A total of 427 patients (274 males, 153 females) were studied and the mean age was 59 years. Renal artery narrowing was identified in 10.5% of patients. Significant (> or = 50% diameter narrowing) renal artery stenosis was found in 24 patients (5.6%) and insignificant stenosis was found in 21 patients (4.9%). Significant unilateral stenosis was present in 4.2% of patients and bilateral stenosis was present in 1.4%. The stem of the renal artery was a more common site of stenosis in 62.2% of patients than in the ostium (37.8%), but the severity of stenosis was not significantly different according to the site of stenosis. By univariate and multivariate logistic regression analysis, the association of clinical variables with renal artery stenosis was assessed. Multivariable predictors included age, hypertension and peripheral vascular disease (p < 0.05). The variables such as sex, smoking history, hyperlipidemia, renal insufficiency, as well as the presence of obesity, severity of coronary heart disease and D.M., were not associated. In conclusion, the prevalence of angiographically-determined renal artery narrowing in a patient population undergoing cardiac catheterization is 10.5%. Old age, hypertension and evidence of peripheral vascular disease represent the predictors of renal artery stenosis.
Adult ; Aged ; Female ; Heart Catheterization* ; Human ; Hypertension/etiology ; Male ; Middle Age ; Multivariate Analysis ; Prevalence ; Renal Artery Obstruction/etiology ; Renal Artery Obstruction/epidemiology* ; Risk Factors

Treatment of nephrotic syndrome associated with hepatitis B are controversial, but some patients may respond to interferon therapy. Steroid therapy in these patients could be limited, because it may aggravate hepatitis with the acute viral replication. Lamivudine may also be effective in reducing viral burden and may convert patients from HBsAg and HBeAg positive to negative. But there was no report for the usefulness of lamivudine in treatment of these patients. We performed a randomized comparative study to assess the usefulness of lamivudine and the effect of steroid in the use of lamivudine in treatment of B-viral associated nephrotic syndrome. Twelve patients(M:F=1:0.2, mean age 34.3 years, MCD 1, MPGN 5, MGN 6 patients) suspected to have the acute viral replication with nephrotic syndrome were included. They were randomly assigned to receive lamivudine and steroid combination therapy(group I, 150mg of lamivudine with high-dose steroid, 1mg/kg/day, orally once daily in 6 patients) or lamivudine alone therapy(group II, 150 mg of lamivudine orally once daily alone in 6 patients). The duration of lamivudine use was 6 months in both groups, and that of steroid use was 6 weeks in group 1. Then, lamivudine and steroid were tapered according to the amount of proteinuria and serum HBV-DNA titer. All patients were closely monitored every 2 months with clinical, bioche mical, and serological parameters for 10 months. The rate of negative sero-conversion of HBV- DNA were 91.7%(11/12) at 2 months of lamivudine therapy in all patients, and there was no difference between group I and II(83.3% vs. 100%, p>0.05). In group I, there were a significant decreases of mean serum HBV-DNA values(899.2+/-711.9 vs. 31.4+/-32.7, 12.7+/-27.6, and 137.2+/-278.1pg/ml, p<0.05, respectively), proteinuria(11.0+/-3.6 vs. 3.9+/-2.3, 2.1+/-2.3, and 2.5+/-3.1g/d, p<0.05, respectively), and SGPT (57.7+/-18.9 vs. 30.5+/-12.4, 23.8+/-10.2, and 26.0+/-10.4 IU/L, p<0.05, respectively) measured at 2, 6, and 10months compared to before therapy, and serum albumin levels were significantly increased at 2, 6, and 10months compared to before therapy(2.2+/-0.5 vs. 3.1+/-0.5, 3.9+/-0.8, and 3.9+/-0.9g/dL, p<0.05, respectively). In group II, serum HBV-DNA was significantly decreased at 2, 6, and 10 months compared to before therapy(358.8+/-369.3 vs. 19.1+/-27.0, 0.0+/-0.0, and 0.0+/-0.0pg/ml, p<0.05, respectively), and proteinuria and SGPT were significantly decreased at 6 and 10 months compared to before therapy(8.5+/-5.5 vs. 2.6+/-1.3 and 2.1+/-2.3g/d, p<0.05; 67.5+/-43.0 vs. 25.3+/-11.6 and 31.5+/-9.2IU/L, p<0.05, respectively). Serum albumin levels were significantly increased at 10 months compared to before therapy(2.8+/-0.8 vs. 4.3+/-0.1g/dL, p<0.05). Serum HBV-DNA levels rebounded in two patients of group I, but none was observed in group II. No serious adverse events were observed in all the patients. In conclusion, lamivudine and steroid combination therapy may more rapidly decrease proteinuria than lamivudine alone in B-viral associated nephrotic syndrome, but may induce the rebound of serum HBV-DNA.
Alanine Transaminase ; DNA ; Glomerulonephritis, Membranoproliferative ; Hepatitis B e Antigens ; Hepatitis B Surface Antigens ; Hepatitis B virus ; Hepatitis B* ; Hepatitis* ; Humans ; Interferons ; Lamivudine* ; Nephrotic Syndrome* ; Proteinuria ; Serum Albumin ; Viral Load