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The aim of this study was to examine the altering patterns in clinical characteristics and severity of acute post-streptococcal glomerulonephritis (APSGN) in children.We analyzed the medical records of 119 children who were diagnosed with APSGN from 1987 to 2018, retrospectively. The patients were divided into two groups: Group I (n=72, before 1998) and Group II (n=47, after 1998). Clinical, radiologic, and laboratory findings were compared between the two groups.The clinical manifestations, including vomiting (20.8% vs. 4.3%, p=0.014), oliguria (40.3% vs. 19.1%, p=0.016), and generalized edema (86.1% vs. 63.8%, p=0.005), were statistically less frequent since 1998. Pulmonary edema on chest X-ray (22.7% vs. 4.4%, p=0.014) was less frequent in Group II than in Group I. The level of BUN (23.3±19.3 vs. 18.8±11.2, p=0.009) was lower in Group II than in Group I, while that of creatinine was not significantly different between the two groups. C3 level was an independent factor for predicting the development of edema (odds ratio [OR]: 1.034, 95% CI: 1.010-1.060, p=0.006) and acute nephritic symptoms (≥2) (OR: 0.974, 95% CI: 0.952-0996, p=0.020). It was also negatively correlated with an increasing number of acute nephritic symptoms, including oliguria and edema, in patients with APSGN (R=-0.182, p=0.048).This study demonstrated that APSGN had favorable clinical manifestations and severity over the past 30 years. The monitoring of C3 levels can be used to assess the disease severity and risk of complications, including edema and oliguria, which are decreasing in South Korean children.

Catheter probe endoscopic ultrasonography (C-EUS) by ultrasonographic jelly-filled method has been used to evaluate esophageal subepithelial tumors (SETs). Ultrasonographic jelly is safe on the skin, but its internal safety has not been demonstrated. The jelly stored at room temperature is easily injected into the esophagus through the instrument channel of the endoscope. However, using jelly stored at room temperature remains problematic because the jelly is drained rapidly. We used cold lubricating jelly and an intravenous extension tube to resolve these problems. In this study, we evaluated the safety and efficacy of cold lubricating jelly-filled method. The medical records of patients who underwent C-EUS by using water or cold lubricating jelly-filled method for esophageal SETs from March 2013 to September 2016 in Gangneung Asan hospital were reviewed. Clinical characteristics and EUS findings were evaluated retrospectively. Image quality and procedure time between water and cold lubricating jelly-filled method were compared retrospectively. This study included 138 patients (74 males, 64 females) with esophageal SET with a mean age of 57.1 ± 11.1 years. Thirty-four patients had lesions in the upper esophagus, 58 patients had lesions in the middle esophagus, and 46 patients had lesions in the lower esophagus. The EUS diagnoses were leiomyoma (82.6%), hemangioma (4.3%), extrinsic compressive lesion (3.6%), granulosa cell tumor (2.9%), ectopic calcification (1.4%), cyst (1.4%), lipoma (0.7%), varix (0.7%), and inconclusive lesion (2.2%). The mean image score in the cold lubricating jelly filled-method group was higher than that in the water-filled method group (3.2 ± 0.7 vs. 2.8 ± 0.7, P = 0.002). The procedure time in the cold lubricating jelly filled-method group was shorter than that in the water-filled method group (10 minutes 27 seconds ± 4 minutes 22 seconds versus 13 minutes 20 seconds ± 6 minutes 20 seconds, P = 0.045). No procedure-related complication was observed. C-EUS using the cold lubricating jelly-filled method seems to provide better image quality and shorter procedure time compared with C-EUS using the water-filled method.

SummaryBackground Non-alcoholic fatty liver disease (NAFLD) is known to be associated with polycystic ovary syndrome (PCOS). However, most studies investigated the prevalence of NAFLD in obese PCOS patients. Aim To compare the prevalence of non-obese NAFLD in women with or without PCOS, and to assess an independent association between PCOS and NAFLD in a non-obese Asian cohort. Methods This was a case–control study using a prospective PCOS cohort. After subjects with other potential causes of chronic liver disease were excluded, 275 non-obese women with PCOS and 892 non-obese controls were enrolled. NAFLD was determined by hepatic ultrasonography. Main outcomes were the prevalence of NAFLD on hepatic ultrasonography between non-obese women with or without PCOS, and an independent association between non-obese NAFLD and PCOS. Results Non-obese women with PCOS had a significantly higher prevalence of NAFLD than those without PCOS (5.5% vs. 2.8%, P = 0.027). PCOS was associated with non-obese NAFLD (odds ratio: 2.62, 95% confidence intervals: 1.25–5.48) after adjustment for age and body mass index (BMI). In women with PCOS, the level of androgenicity represented by free testosterone or free androgen index was associated with NAFLD after adjustment for age, BMI, lipid profile, insulin resistance or glycaemic status. Conclusions Non-obese NAFLD is more prevalent in women with polycystic ovary syndrome than in those without. In non-obese patients with polycystic ovary syndrome, hyperandrogenemia may be an independent risk factor for non-obese NAFLD.

Detailed, country‐specific epidemiological data are needed to characterize the burden of chronic hepatitis C virus (HCV) infection around the world. With new treatment options available, policy makers and public health officials must reconsider national strategies for infection control. In this study of 15 countries, published and unpublished data on HCV prevalence, viraemia, genotype, age and gender distribution, liver transplants and diagnosis and treatment rates were gathered from the literature and validated by expert consensus in each country. Viraemic prevalence in this study ranged from 0.2% in Iran and Lebanon to 4.2% in Pakistan. The largest viraemic populations were in Pakistan (7001000 cases) and Indonesia (3187000 cases). Injection drug use (IDU) and a historically unsafe blood supply were major risk factors in most countries. Diagnosis, treatment and liver transplant rates varied widely between countries. However, comparison across countries was difficult as the number of cases changes over time. Access to reliable data on measures such as these is critical for the development of future strategies to manage the disease burden.

The total number, morbidity and mortality attributed to viraemic hepatitis C virus (HCV) infections change over time making it difficult to compare reported estimates from different years. Models were developed for 15 countries to quantify and characterize the viraemic population and forecast the changes in the infected population and the corresponding disease burden from 2014 to 2030. With the exception of Iceland, Iran, Latvia and Pakistan, the total number of viraemic HCV infections is expected to decline from 2014 to 2030, but the associated morbidity and mortality are expected to increase in all countries except for Japan and South Korea. In the latter two countries, mortality due to an ageing population will drive down prevalence, morbidity and mortality. On the other hand, both countries have already experienced a rapid increase in HCV‐related mortality and morbidity. HCV‐related morbidity and mortality are projected to increase between 2014 and 2030 in all other countries as result of an ageing HCV‐infected population. Thus, although the total number of HCV countries is expected to decline in most countries studied, the associated disease burden is expected to increase. The current treatment paradigm is inadequate if large reductions in HCV‐related morbidity and mortality are to be achieved.

1 Poisoning is a common reason for presentation to hospital and hospital admission but there is no agreed policy for managing these patients. This study exam ined the management of patients presenting with poisoning and the factors affecting the probability of hospital admission and prolonged stay. 2 Data on all cases of poisoning presenting to six Accident and Emergency departments in the North East of England over 12 weeks in 1994 was collected prospectively from A&E notes. Length of stay and outcome were recorded from hospital computer records. 3 Overall, 73% of patients were admitted to a medical ward. Probability of admission was not independently affected by age or gender but was increased in those with intentional poisoning (Odds Ratio (OR) 3.3 [95% CI 1.8, 6.1]), a history of self harm (OR 1.7, [1.0, 2.9]) or potentially hazardous poisoning (OR 3.7 [2.1, 6.6]). There were significant variations between hospitals (50 - 80%) which could not be attributed to case mix. 4 Prolonged stay ( > 2 nights) was more common in patients over 65 years (OR 6.8 [2.9, 16.1]), those with intentional poisoning (OR 2.7 [1.1, 6.6]) and those with potentially hazardous poisoning (OR 2.6 [1.4, 4.9]). Mean hospital stay was 1.5 days and varied signifi cantly between hospitals from 0.8 to 2.1 days and this was independent of case mix. 5 There are appreciable variations in the management of poisoning between hospitals which are not explained by patient characteristics. Savings would occur if rates of admission and duration of stay were reduced by those hospitals where admission is more frequent or hospital stay is longer. However, the impact of this on long term morbidity is unknown.

Dysregulation of cyclin expression has been reported for several human malignancies, including breast cancer. To further investigate the role of cyclin genes in mammary tumorigenesis we analyzed the expression of cyclins D1, E and A and other cell cycle-related proteins in a series of nine N-methyl-N-nitrosourea-induced primary rat mammary tumors. Western blot analysis revealed a 10- to 15-fold increase in the level of cyclin D1 protein in most (7/9) of the tumors, when compared with normal rat mammary gland. The two tumors that did not show this increase also displayed negligible levels of the retinoblastoma protein. A moderate increase, 1.5- to 2-fold, in the level of cyclin E was observed in four tumors and three tumors displayed abnormal low molecular weight cyclin E-related proteins. None of the tumors showed amplification of the cyclin D1 or E genes when studied by Southern blot analysis. All nine tumors showed a 2- to 6-fold increase in the level of cyclin A protein. Most of the tumors also displayed a marked increase in levels of the CDK2 and CDK4 proteins. These changes did not appear to be simply a consequence of increased cell proliferation, as assessed by proliferating cell nuclear antigen analysis. Thus, aberrant expression of cyclins and other cyclin-related genes occurs frequently in mammary tumorigenesis in both rodents and humans.

To assess the association between high body mass index (BMI) and treatment response in recent-onset rheumatoid arthritis.In the Behandelstrategieën voor Reumatoide Artritis (Treatment Strategies for Rheumatoid Arthritis) study, 508 patients were randomized to initial monotherapy or combination therapy with prednisone or infliximab (IFX). The response to Disease Activity Score (DAS) ≤2.4-steered treatment (first dose and after 1 year) was compared between patients with a BMI25 kg/m(2) and ≥25 kg/m(2) , using relative risk (RR) regression analyses. DAS, components of DAS, and functional ability during the first year were compared using linear mixed models.High BMI was independently associated with failure to achieve a DAS ≤2.4 on initial therapy (RR 1.20 [95% confidence interval (95% CI) 1.05, 1.37]). The effect for combination therapy with prednisone was RR 1.55 (95% CI 1.06, 2.28) and for combination therapy with IFX 1.42 (95% CI 0.98, 2.06). The RRs for failure after 1 year were 1.46 (95% CI 0.75, 2.83) and 2.20 (95% CI 0.99, 4.92), respectively. High BMI was also associated with failure on delayed combination therapy with IFX, after adjustment for selection bias related to previous failure on disease-modifying antirheumatic drugs. No significant association was observed in the initial monotherapy groups. In the first year, patients with a high BMI had higher DAS and worse functional ability, with more tender joints and a higher visual analog scale global health, but not more swollen joints and similar systemic inflammation.High BMI was independently associated with failure to achieve low DAS on initial combination therapy with prednisone and on initial and delayed treatment with IFX. Patients with a high BMI experienced more pain, but not more swelling or systemic inflammation.

STUDY OBJECTIVE--To investigate the numbers and characteristics of patients with ophthalmological accidents and emergencies presenting to hospitals. DESIGN--Prospective survey over eight weeks. SETTING--Two general and one ophthalmic accident and emergency departments, two general outpatient departments, and an eye hospital ward consulting room (all in two teaching hospitals) in Newcastle upon Tyne. MEASUREMENTS AND MAIN RESULTS--Consultation numbers by age, sex, health district of residence, source of referral, diagnosis, and disposal were determined. An average of 37 ophthalmological emergency patients were seen daily. The all cause consultation rate per 1000 population for Newcastle residents was 2.64 (17.2 per year); for injuries it was 1.10 (7.2 per year) and for inflammations the rate was 0.91 (5.9 per year). Consultation rates per 1000 were 3.5 for males and 1.8 for females, the excess being explained by the higher risk of injury to men. Most patients were self-referred (58%), consulted during office hours (79.6%), were attended by senior house officers working alone (83.9%), and were asked to return for follow up (66.1%). Patients in an accident and emergency department seldom saw a consultant in their initial management. The diagnoses of patients from outside Newcastle were little different from those who lived within the city. The 10 commonest problems accounted for 68% of all cases. Injuries were the commonest problem (40.9% of all diagnoses). CONCLUSION--Ophthalmological accident and emergencies are an important component of an accident and emergency department workload. These patients are usually seen by junior doctors, some untrained in ophthalmology. The wide range of presenting problems poses a challenge for training and the organisation of effective referral chains, while the gender difference in injury rates points to the potential for prevention.

Interquartile range/median value (IQR/M) of liver stiffness measurement (LSM) is a factor in chronic hepatitis C (CHC) leading to over estimation of fibrosis by Fibroscan.To investigate factors that affect the accuracy of LSM in chronic hepatitis B (CHB).One hundred and ninety-nine patients were enrolled. Only procedures yieldingor =10 valid measurements were considered reliable. Liver fibrosis was evaluated using the Batts and Ludwig system. Liver biopsy (LB) specimens15 mm were considered ineligible.The mean age (142 men and 57 women) was 40.1 years. A significant discordance (discordance of at least two stages between LB and LSM) was identified in 38 (19.1%) and 47 (23.6%) patients respectively, according to Marcellin et al. and Chan et al.'s cutoff values. In multivariate analyses, BMI and fibrosis stage (F0-2 vs. F3-4) were identified as independent predictors for significant discordance (P = 0.040; hazard ratio [HR], 1.126; 95% confidence interval [CI], 1.005-1.261 and P = 0.036; HR, 0.450; 95% CI, 0.213-0.949 respectively) with Marcellin et al.'s cutoffs, whereas fibrosis stage was the only independent predictor (P = 0.004; HR, 0.300; 95% CI, 0.131-0.685) with Chan's cutoffs.Success rate and IQR/M were not predictive factors of the accuracy for diagnosing liver fibrosis by Fibroscan in CHB. Fibrosis stage (F0-2) was the only factor to predict significant discordance between LB and LSM.

The Ottawa ankle rules are a clinical instrument calibrated towards a high sensitivity in order not to miss any fractures of the ankle or mid-foot. This is at the cost of a mean specificity of around only 32%. The aim of this study was to determine the suitability of tuning fork testing in combination with existing Ottawa guidance for increasing the specificity in detecting fractures of the lateral malleolus. A prospective pilot study was carried out, in which a single trained investigator examined all patients with already "Ottawa positive" findings for possible lateral malleolus injury by applying a tuning fork (C(o) 128 Hz). The tuning fork test findings were compared with formal reports of plain ankle radiographs using simple cross-table analysis. The observed prevalence of ankle fractures was 5 of 49 (10%). Sensitivity and specificity were calculated as 100% and 61%, respectively, for tuning fork testing on the tip of the lateral malleolus (TLM), and as 100% and 95%, respectively, for testing on the distal fibula shaft (DFS). The associated positive and negative likelihood ratios were 2.59 and 0 (TLM), and 22 and 0 (DFS), respectively. The data were significant, with p = 0.014 (TLM) and p

AIMS: The expression of TGF beta-inducible gene h3(beta ig-h3) has been used to assess the biological activity of TGF beta in the kidney. In this study, we investigated whether the urinary concentration of beta ig-h3 is associated with diabetic nephropathy in patients with Type 2 diabetes mellitus. We also evaluated the relationship between the urinary concentration of beta ig-3 and proteinuria and microalbuminuria (AER) in a normal healthy population and in Type 2 diabetes patients. METHODS: Four hundred and seventy-nine Type 2 diabetic patients without non-diabetic kidney diseases and 528 healthy control subjects were enrolled. The study subjects were divided into five groups: a non-diabetic healthy control group with normal ACR (n = 443), a non-diabetic healthy control group with microalbuminuria (n = 85), a normoalbuminuric diabetic group (n = 198), a microalbuminuric diabetic group (n = 155) and an overt proteinuria group (n = 126). Urinary levels of beta ig-h3 were measured by enzyme-linked immunosorbent assay. RESULTS: (i) Urinary excretion of beta ig-h3 was significantly higher in the diabetic groups than in the controls, even in the normoalbuminuric stage (25.02 +/- 8.84 vs. 18.67 +/- 6.56, P = 0.03). In diabetic patients, urinary beta ig-h3 levels increased significantly as diabetic nephropathy advanced (25.02 +/- 8.84 vs. 34.06 +/- 24.55 vs. 169.63 +/- 57.33, P < 0.001). (ii) Proteinuria was found to be significantly correlated with urinary beta ig-h3 (healthy control; r = 0.137, P = 0.019, diabetic patients; r = 0.604, P < 0.001). ACR was also found to be significantly related with urinary beta ig-h3 in diabetic patients (r = 0.383, P = 0.006). (iii) In diabetic patients, urinary beta ig-h3 was significantly related with systolic and diastolic blood pressure (systolic blood pressure: r = 0.436, P = 0.024; diastolic blood pressure, r = 0.365, P = 0.042), total cholesterol and HbA(1c) (cholesterol: r = 0.169, P = 0.03, HbA(1c); r = 0.387, P = 0.044). Logistic regression analyses showed that urinary beta ig-h3 was associated with a significant increase in the risk of microalbuminuria and proteinuria in diabetic patients. CONCLUSIONS: Longitudinal monitoring of urinary beta ig-h3 may improve the likelihood of detecting diabetic nephropathy at an earlier stage and beta ig-h3 could be a sensitive marker of diabetic kidney disease progression.

Aims Vascular endothelial growth factor (VEGF) has been implicated in the pathogenesis of diabetes mellitus. We determined whether alterations of plasma and urinary VEGF levels are related to diabetic nephropathy in Type 2 diabetic patients. Methods One hundred and seven patients and 47 healthy controls were studied. Study subjects were divided into four groups using urinary albumin-to-creatinine ratio (ACR): a non-diabetic healthy control group (n = 47), a normoalbuminuric diabetic group (n = 37), a microalbuminuric diabetic group (n = 37) and an overt proteinuric diabetic group (n = 33). VEGF levels were measured by enzyme-linked immunosorbent assay. Results (i) Urinary VEGF concentrations were significantly higher in the diabetic groups, even at the normoalbuminuric stage (log VEGF/Cr, normoalbuminuria; 4.33 ± 1.06 vs. control; 3.53 ± 0.79, P = 0.009). Urinary VEGF excretions increased as diabetic nephropathy advanced. (ii) Plasma and urinary VEGF levels were higher in hypertensive diabetic patients than in the normotensive individuals with diabetes. (iii) In those with diabetes, plasma VEGF levels were found to be positively correlated with plasma urea (r = 0.398, P = 0.039) and urinary ACR (r = 0.251, P = 0.044), and urinary VEGF to be positively correlated with urinary ACR (r = 0.645, P

AIM: There are still insufficient clinical reports concerning quality-switched Nd:YAG laser (QSNYL) in the treatment of superficial pigmented lesions in Asians. The purpose of this study was to analyse the efficacy and side effect profiles of QSNYL-assisted pigment removal in brown skin. METHODS: A total of 71 patients, presenting a wide gamut of superficial epidermal lesions, were treated with QSNYL. Clinical responses were assessed by comKeywords: paring photographs that were taken serially in every treatment. RESULTS: Treatment using the QSNYL is reported individually for the various superficial pigmented lesions in the skin of Korean patients. CONCLUSION: QSNYL may be a beneficial alternative tool for the treatment of a number of benign pigmented lesions including freckles, lentigines and unilateral lentiginosis.

Although the mechanism of susceptibility to chronic persistent hepatitis B virus (HBV) infection is not well clarified, immunogenetic factors of the host may have a role. Recently, a strong association between HLA-DR13 and the self-limited course of HBV infection has been reported. To determine whether the elimination of HBV is related to a particular HLA allele, we studied the HBV markers and HLA-DR phenotypes of 1,272 Koreans who had visited Yonsei University Medical Center for renal transplantation. They included 330 renal transplant donors. Subjects were categorized into 3 different groups: the "Unexposed Group" (UE; n = 946) with negative HBV markers, the "Chronic Carrier Group" (CC; n = 83), who were hepatitis B surface antigen (HBsAg)-positive, and the "Spontaneously Cleared Group" (SC; n = 243), who were HBsAg-negative with antibodies to HBsAg (anti-HBs) and hepatitis B core antigen (anti-HBc). HLA-DR4 was the most common type in all groups. HLA-DR6 was significantly more frequent in 69 of 243 subjects with SC (28. 4%) than in 8 of 83 subjects with CC (9.6%) (P.001; relative risk [RR] = 3.72). HLA-DR9 was significantly more frequent in CC than in SC (P.001; RR = 0.33). HLA-DR13 showed a stronger association with the clearance of HBV than the other HLA-DR6 subgroup. The distribution of HLA-DR phenotypes was similar regardless of renal disease. Our data indicate that HLA-DR6, especially HLA-DR13, is one of the host factors, which influences the immune response to HBV, and may be associated with self-elimination of HBV in Koreans.

The low-density lipoprotein (LDL) receptor gene from 80 unrelated Korean patients with familial hypercholesterolemia (FH) was analyzed to screen for small structural rearrangements that could not be detected by Southern blot hybridization. Three different small deletions were detected in exon 11 of 3 FH patients and were characterized by DNA sequence analysis. Of them two mutations are in-frame 36-bp (FH 2) and 9-bp (FH 34) deletions that result in the loss of twelve amino acids (from Met510 to Ile521) and three amino acids (Thr513, Asp514 and Trp515), respectively. Both mutations are located in the third of the five YWTD motifs of the LDL receptor gene. The third mutation (FH 400) is a 2-bp deletion that shifts the translational reading frame and results in a prematurely terminated receptor protein. The generation of a 36-bp deletion can be explained by the formation of a hairpin-loop structure mediated by inverted repeat sequences. On the other hand, the mechanism responsible for the 9- and the 2-bp deletions is probably strand-slippage mispairing mediated by short direct repeats. All of these three deletions are novel mutations. Each of the three deletions was detected only in a single pedigree out of 80 FH families analyzed.

Monocytes are recruited from the circulation into the subendothelial space where they differentiate into mature macrophages and internalize modified lipoproteins to become lipid-laden foam cells. The accumulation of monocytes is mediated by the interaction of locally produced chemoattractant protein-1 (MCP-1) with its receptor CCR2. The objective of the present study is to demonstrate the differential effects of plasma lipoproteins on monocyte CCR2 expression. The CCR2 expression was increased about 2.4-fold in monocytes isolated from hypercholesterolemic patients, compared to monocytes from normal controls. There was a significant correlation between CCR2 expression and plasma low density lipoprotein (LDL). Elevated levels of high density lipoprotein (HDL) blunted and even reverted the effects of LDL on CCR2 expression, both in vivo and in vitro. The causal relationship between plasma lipoproteins and CCR2 expression was further confirmed by modulating the lipoprotein profile. Estrogen supplement therapy decreased plasma LDL cholesterol, increased plasma HDL cholesterol, and reduced CCR2 expression in hypercholesterolemic postmenopausal women, but had no effect on the plasma lipid profile or CCR2 expression in normocholesterolemic subjects. The physiological significance of altered CCR2 expression was tested by chemotaxis assay, and our results demonstrated that treatment of THP-1 monocytes with LDL induced CCR2 expression and substantially enhanced the chemotaxis elicited by MCP-1. Our findings suggest that plasma lipoproteins differentially control monocyte function and that monocytes from hypercholesterolemic subjects are hyperresponsive to chemotactic stimuli. This may increase their accumulation in the vessel wall and accelerate the pathogenic events of atherogenesis.

The neutrophilic dermatoses are significantly associated with myeloid malignancies. We now describe the clinical and histological features of 11 patients with these disorders, namely Sweet's syndrome in three cases, pyoderma gangrenosum in two, and neutrophilic eccrine hidradenitis in one; there were also five others which could not be categorised as recognised entities. Our observations, as well as those from a review of the literature, support the hypothesis that in the neutrophilic dermatoses associated with myeloid malignancy, a common mechanism may be involved.

Nonsteriodal anti-inflammatory drugs (NSAIDs) are among the most commonly used medications in the United States and elsewhere, mainly for the treatment of arthritis. The NSAID sulindac causes regression and prevents the recurrence of premalignant colonic polyps in patients with familial adenomatous polyposis and inhibits colon carcinogenesis in rodents. Sulindac and sulindac sulfone, a metabolite of sulindac that lacks cyclooxygenase (cox) inhibitory activity, also inhibit mammary carcinogenesis in rats. To obtain insights into the relevance of these findings to human breast cancer, we examined the mechanism of action of sulindac and its sulfide and sulfone metabolites on the normal human mammary epithelial cell line MCF-10F and the human breast cancer cell line MCF-7. Of the three compounds, the sulfide was the most potent inhibitor of cell growth, although the sulfone and sulfoxide were also active at higher concentrations. Treatment of MCF-10F and MCF-7 cells with 100 microM sulindac sulfide resulted in accumulation of cells in the G1 phase of the cell cycle and induction of apoptosis. Apoptosis occurred within 24 h as determined by the TUNEL assay and DNA laddering was observed at 72 h. The accumulation of cells in G1 was associated with decreased levels of expression of cyclin D1 but no effect was seen on the expression of CDK4 or the immediate early response gene c-jun. Treatment with sulindac sulfide caused a striking induction of the CDK inhibitor p21WAF1 in MCF-10F cells. The MCF-7 cell line expressed a high basal level of p21WAF1 which did not change significantly after drug treatment. The pro-apoptotic gene BAX was not induced in either MCF-10F or MCF-7 cells by sulindac sulfide. Stable overexpression of cyclin D1, which frequently occurs in breast cancers, did not protect mammary epithelial cells from inhibition by the sulfide. These studies suggest that this class of compounds warrants further study with respect to breast cancer prevention and treatment.

1 A 12 week prospective survey of all patients of any age with confirmed or suspected poisoning presenting to six accident and emergency departments in the North East of England was performed to establish the local incidence and patterns of presentation of poisoning.2 945 episodes of poisoning involving 852 patients were recorded representing approximately 1.2% of all A&E presentations and suggesting an annual attendance rate of 2.7 per 1000 persons per year.3 Attendance rates varied threefold between hospitals and were similar in males and females overall; between the ages of five and 14 attendances were more common in females (1.9 vs 0.6/103/y) while between 0 and 4 y (3.1 vs 2.4) and 25 and 34 y (3.9 vs 2.9/103/y) they were more common in males.4 The median interval between poisoning and presenta tion was 2 h (mean 4.1 h) and only 19% of cases presented within 1 h. Presentation was most common between Friday evening and Tuesday morning and in the late afternoon and evening.5 6% of the patients presented more than once with poisoning during the study period and 37% had a past history of deliberate self-harm. The most common poisons involved were paracetamol (43%), opioids (15%) and benzodiazepines (15%).6 The study illustrates the frequency of presentations of poisoning to A&E departments. The high rate of poisoning in young men and the increasing use of paracetamol are particular causes for concern.

Ten patients with hepatitis C virus (HCV) infection (experimental group) were treated with interferon-alpha (IF-alpha). Dosage was six million units per day for one week and then three times a week for another six months. Seven HCV-infected patients (control group) did not receive IF-alpha therapy. The hypervariable region (HVR) of HCV in the sera of patients was amplified by reverse transcription-polymerase chain reaction (RT-PCR), and the variation of amino acid sequence in this region was determined. Serum alanine aminotransferase (ALT) activities in five patients treated for six months with IF-alpha fell to the normal range, when HCV was not detected in the sera of three patients. The nucleotide sequence variation in HVR of HCV in the sera of five patients who responded well to the IF-alpha therapy was relatively less than that in another five patients who did not respond to IF-alpha therapy and those in the control patients. These results indicate that the effectiveness of IF-alpha therapy was related to the sequence variation of HVR of HCV. This may have resulted from the selection pressure by humoral antibodies directed to HVR of HCV. It is concluded that the higher rate of sequence variation in HVR of HCV was compatible with a lower degree of effectiveness of IF-alpha therapy.

Prednisone is frequently used in the treatment of elderly-onset rheumatoid arthritis (RA), but the balance between efficacy and toxicity, including the effect on bone mass, has not been investigated in long-term studies. This prospective, randomized study was undertaken to compare disease activity and bone mass during long-term treatment with prednisone versus chloroquine in this patient population.Patients with active RA diagnosed at ageor = 60 were randomized to receive prednisone (15 mg/day for 1 month, with the dosage tapered as low as possible thereafter) (n = 28) or chloroquine (n = 28). Patients who did not show a response received other second-line drugs as an adjunct to prednisone or as a replacement for chloroquine. Bone mass was measured by dual-energy x-ray absorptiometry. The study duration was 2 years.During the 2 years, treatment with other second-line drugs was needed for 12 patients in the prednisone group (43%) and 8 in the chloroquine group (29%). Functional capacity and disease activity improved significantly in both groups and did not differ significantly between the groups, except for a greater improvement in the prednisone group at 1 month. Radiographic scores for joint destruction progressed similarly in both groups. There was a nonsignificant excess bone loss of 1.8% in the spine and 1.5% in the hip in the prednisone group, compared with the chloroquine group.Neither treatment was entirely satisfactory since a significant number of patients needed an additional second-line drug over the 2-year period.

A prospective study was carried out to assess the incidence of recurrent soft tissue injuries to the ankle joint. Out of 310 patients with acute ankle injuries seen in the accident and emergency department at the Royal Victoria Infirmary, Newcastle upon Tyne, 101 (32.5%) had injuries which were severe enough to necessitate review in the follow-up clinic. Twenty-seven of these patients (26.7%) had sustained one or more previous injuries to the same ankle within the past 24 months. This rather high incidence of recurrence highlights the need to evaluate our current diagnostic and treatment policies in dealing with this common injury.

A propos d'un cas de fracture de fatigue du tibia puis du perone au niveau de la cheville. Aucune cause medicale n'a ete retrouvee

1 Paracetamol is increasingly involved in self-poisoning in the United Kingdom and remains a common cause of fatal poisoning. 2 To document the epidemiology and early management of paracetamol poisoning data were collected on consecutive patients with suspected paracetamol poisoning presenting to 6 hospitals in the North East of England over 12 weeks in 1994. 3 There were 400 presentations (attendance rate 1.14/103 population/yr) involving 343 persons (45% male). Paracetamol concentrations at 4 h correlated weakly with reported paracetamol dose (R=0.49, P < 0.0001) and were similar comparing those treated and not treated by gastric decontamination. 4 In 38 (9%) cases paracetamol concentrations were above the appropriate nomogram treatment line, including 3% and 20% of patients who reported ingesting less than and more than 12 g respectively. In 21 patients acetylcysteine treatment was deferred until admission to the ward, the mean delay involved was 2.8 h. 5 One patient died, from arrhythmias caused by co- ingested dothiepin. 6 Paracetamol poisoning is common. Most cases do not have potentially toxic plasma paracetamol concentra tions, but those who do often present late and antidotal treatment may be delayed inappropriately.