Risk of herpesvirus, serious and opportunistic infections in atopic dermatitis: a population-based cohort study.

BACKGROUND: Staphylococcal and herpes simplex virus (HSV) infections are commonly recognized in atopic dermatitis (AD), but less is known about other types of infections. OBJECTIVES: To determine the risk of herpesvirus infections, serious infections and opportunistic infections in patients with AD. METHODS: We conducted a population-based cohort study using UK-based electronic medical records data. Patients with AD were each matched to up to five unaffected patients on age, practice and index date. AD severity was defined using treatments as a proxy. Outcomes were incident herpesvirus infections [cytomegalovirus (CMV), Epstein-Barr virus (EBV), HSV or varicella zoster virus (VZV)], serious infections and opportunistic infections. RESULTS: Among 409 431 children and 625 083 adults with AD matched to 1 809 029 children and 2 678 888 adults without AD, respectively, adjusted Cox regression models showed children and adults with AD had a 50-52% greater risk of HSV and 18-33% greater risk of VZV, with risk increasing in parallel with AD severity. CMV risk was elevated among children with AD [hazard ratio (HR) 2·50, 95% confidence interval (95% CI) 1·38-4·54] and adults with severe AD (HR 4·45, 95% CI 1·76-11·25). Patients with AD had a 26-40% increase in risk of serious infections, with severe AD carrying the greatest risk. Although rare, opportunistic infections were associated with all severities of AD in adults (overall HR 1·31, 95% CI 1·20-1·42), but were not associated with AD in children. All estimates remained consistent after excluding patients receiving immunosuppressive treatments for AD. CONCLUSIONS: AD is significantly associated with herpesvirus infections, serious infections and opportunistic infections in a 'dose-dependent' manner with increasing severity. AD may increase susceptibility to infections exclusive of immunosuppressive medications.

A randomized phase III trial comparing adjuvant single-agent S1, S-1 with oxaliplatin, and postoperative chemoradiation with S-1 and oxaliplatin in patients with node-positive gastric cancer after D2 resection: the ARTIST 2 trial☆.

BACKGROUND: Adjuvant chemotherapy and chemoradiotherapy are some of the standards of care for gastric cancer (GC). The Adjuvant chemoRadioTherapy In Stomach Tumors (ARTIST) 2 trial compares two adjuvant chemotherapy regimens and chemoradiotherapy in patients with D2-resected, stage II or III, node-positive GC. PATIENTS AND METHODS: The ARTIST 2 compared, in a 1:1:1 ratio, three adjuvant regimens: oral S-1 (40-60 mg twice daily 4 weeks on/2 weeks off) for 1 year, S-1 (2 weeks on/1 week off) plus oxaliplatin 130 mg/m2 every 3 weeks (SOX) for 6 months, and SOX plus chemoradiotherapy 45 Gy (SOXRT). Randomization was stratified according to surgery type (total or subtotal gastrectomy), pathologic stage (II or III), and Lauren histologic classification (diffuse or intestinal/mixed). The primary endpoint was disease-free survival (DFS) at 3 years; a reduction of 33% in the hazard ratio (HR) for DFS with SOX or SOXRT, when compared with S-1, was considered clinically meaningful. The trial is registered at clinicaltrials.gov (NCT0176146). RESULTS: A total of 546 patients were recruited between February 2013 and January 2018 with 182, 181, and 183 patients in the S-1, SOX, and SOXRT arms, respectively. Median follow-up period was 47 months, with 178 DFS events observed. Estimated 3-year DFS rates were 64.8%, 74.3%, and 72.8% in the S-1, SOX, and SOXRT arms, respectively. HR for DFS in the control arm (S-1) was shorter than that in the SOX and SOXRT arms: S-1 versus SOX, 0.692 (P = 0.042) and S-1 versus SOXRT, 0.724 (P = 0.074). No difference in DFS was found between SOX and SOXRT (HR 0.971; P = 0.879). Adverse events were as anticipated in each arm, and were generally well-tolerated and manageable. CONCLUSIONS: In patients with curatively D2-resected, stage II/III, node-positive GC, adjuvant SOX or SOXRT was effective in prolonging DFS, when compared with S-1 monotherapy. The addition of radiotherapy to SOX did not significantly reduce the rate of recurrence after D2 gastrectomy.

Head-to-head trials of systemic psoriasis therapies: a systematic review of study design and maximum acceptable treatment differences.

There is increasing use of head-to-head clinical trials in dermatology when establishing the efficacy of a new treatment. Active comparator trials (ACTs) can be classified into three distinct study trial designs: non-inferiority, equivalence and superiority. A better understanding of the statistical parameters, such as acceptable treatment differences (also known as the margin or delta), is necessary to properly design and interpret findings of active comparator trials (ACTs) in the field of dermatology. Therefore, the objective of this study was to summarize the maximum acceptable treatment differences in clinical trials that examine the efficacy of an oral or biologic psoriasis therapy with an active comparator. We conducted a systematic search using MEDLINE, Scopus, EMBASE, Cochrane Central Register of Controlled Trials, LILACS, Web of Science and ClinicalTrials.gov from inception to 31 August 2017. All ACTs with adult participants that had a primary outcome of the Psoriasis Area and Severity Index score were included. Bibliographies of articles were further reviewed. Two investigators independently assessed for article inclusion and separately completed data extraction of predefined data points. When there was a disagreement, a third investigator was consulted. Of the 49 ACTs included, there were 13 superiority, eight non-inferiority and seven equivalence trials. Another 21 studies had inadequate information for classification. All of the non-inferiority trials reported the margin, one of the superiority and six of the equivalence trials stated the treatment difference explicitly. For superiority trials, acceptable treatment differences ranged from 14% to 20%. The non-inferiority studies reported lower bound margins ranging from -20% to -10%. The equivalence trials reported upper and lower bound margins ranging from ±12.5% to ±18%. The results demonstrate the need for harmonization in the conduct of dermatological clinical trials and in the approaches of reporting research parameters.

Increased prevalence of HCV and hepatic decompensation in adults with psoriasis: a population-based study in the United Kingdom.

BACKGROUND: The hepatitis C virus (HCV) is a major cause of global morbidity and mortality, with conflicting evidence regarding a possible association with psoriasis. OBJECTIVE: To determine the prevalence of HCV in psoriasis patients, compared to controls, and to determine the incidence of hepatic decompensation in HCV+ psoriasis patients compared to HCV+ controls. METHODS: Cross-sectional and cohort studies were conducted in The Health Improvement Network (THIN). RESULTS: In fully adjusted models, a statistically significant increase in prevalence was seen in the adults with psoriasis (OR: 1.24, 95% CI 1.10-1.40). A "dose-response" of HCV prevalence with increasing psoriasis severity was not observed. HCV+ patients with psoriasis had a non-statistically significant increased incidence of hepatic decompensation compared to HCV+ individuals without psoriasis (aHR: 1.58, 95% CI: 0.90-2.77). The risk was highest and statistically significant, in those with moderate-to-severe psoriasis (aHR: 21.51, 95% CI: 7.58-61.03). CONCLUSIONS: These results demonstrate a higher prevalence of HCV in adults with psoriasis and a higher rate of hepatic decompensation in HCV+ individuals with moderate-severe psoriasis.

Comparison of two different S-1 plus cisplatin dosing schedules as first-line chemotherapy for metastatic and/or recurrent gastric cancer: a multicenter, randomized phase III trial (SOS).

BACKGROUND: Five-weekly S-1 plus cisplatin (SP5) is one of the standard first-line regimens for advanced gastric cancer (GC), proven in a Japanese phase III study. To enhance the dose intensity of cisplatin, 3-weekly S-1 plus cisplatin (SP3) was developed. PATIENTS AND METHODS: This multicenter, randomized, open-label, phase III study evaluated whether SP3 (S-1 80 mg/m(2)/day on days 1-14 and cisplatin 60 mg/m(2) on day 1) was noninferior/superior to SP5 (S-1 80-120 mg/day on days 1-21 and cisplatin 60 mg/m(2) on day 1 or 8) in terms of progression-free survival (PFS). Chemotherapy-naive patients with metastatic, recurrent gastric or gastroesophageal junction adenocarcinoma were randomized 1 : 1 to receive either SP3 or SP5. The trial is registered at ClinicalTrials.gov (NCT00915382). RESULTS: Between February 2009 and January 2012, 625 patients were randomized at 42 sites in Korea and Japan. With a median follow-up duration of 32.4 months (range, 13.3-48.6 months) in surviving patients, SP3 was not only noninferior but also superior to SP5 in terms of PFS [median 5.5 versus 4.9 months; hazard ratio (HR) = 0.82; 95% confidence interval (CI) 0.68-0.99; P = 0.0418 for superiority). There was no difference in overall survival (OS) between the groups (median 14.1 versus 13.9 months; HR = 0.99; 95% CI 0.81-1.21; P = 0.9068). In patients with measurable disease, the response rates were 60% in the SP3 arm and 50% in the SP5 arm (P = 0.065). Both regimens were generally well tolerated, but grade 3 or higher anemia (19% versus 9%) and neutropenia (39% versus 9%) were more frequent in SP3. CONCLUSIONS: SP3 is superior to SP5 in terms of PFS. However, since the improvement in PFS was only slight and there was no difference in OS, both SP3 and SP5 can be recommended as first-line treatments for patients with advanced GC.

Patient satisfaction with treatments for moderate-to-severe plaque psoriasis in clinical practice.

BACKGROUND: Treatment satisfaction among patients with moderate-to-severe psoriasis has not been studied and compared across treatments using a validated instrument. OBJECTIVES: To assess patient-reported satisfaction with systemic and phototherapy treatments for moderate-to-severe psoriasis in clinical practice and to correlate satisfaction with disease severity and quality-of-life measures. METHODS: This was a cross-sectional study of 1182 patients with moderate-to-severe psoriasis in the Dermatology Clinical Effectiveness Research Network in the U.S.A. Patients receiving either topical therapies only; monotherapy with oral systemic therapies, biologics or narrowband ultraviolet B phototherapy; or combination therapy with biologics and methotrexate completed the Treatment Satisfaction Questionnaire for Medication version II. RESULTS: Median unadjusted overall satisfaction scores were highest for patients receiving biologic monotherapies, biologic-methotrexate combinations, or phototherapy (83.3); scores were lowest for those receiving topical therapies only or acitretin (66.7). In fully adjusted models, compared with patients receiving methotrexate monotherapy, those receiving adalimumab, etanercept, ustekinumab, phototherapy or adalimumab with methotrexate had significantly higher median overall satisfaction scores by 7.2-8.3 points, while those receiving topical therapies only had significantly lower overall satisfaction by 8.9 points. Adjusted convenience scores were lowest for patients receiving topical therapies only or infliximab. Modest but significant correlations were found between the overall satisfaction subscale and both the Psoriasis Area and Severity Index (ρ = -0.36, P < 0.001) and the Dermatology Life Quality Index (ρ = -0.47, P < 0.001). CONCLUSIONS: Discernible differences were found in treatment satisfaction among therapies, particularly regarding treatment effectiveness and convenience. Further application of treatment satisfaction measures may inform treatment decisions and guideline development.

Validity of The Health Improvement Network (THIN) for the study of psoriasis.

BACKGROUND: Psoriasis is a common disease frequently studied in large databases. To date the validity of psoriasis information has not been established in The Health Improvement Network (THIN). OBJECTIVES: To investigate the validity of THIN for identifying patients with psoriasis and to determine if the database can be used to determine the natural history of the disease. METHODS: First, we conducted a cross-sectional study to determine if psoriasis prevalence in THIN is similar to expected. Second, we created a cohort of 4900 patients, aged 45-64 years, with a psoriasis diagnostic Read Code and surveyed their general practitioners (GPs) to confirm the diagnosis clinically. Third, we created models to determine if psoriasis descriptors (extent, severity, duration and dermatologist confirmation) could be accurately captured from database records. RESULTS: Psoriasis prevalence was 1·9%, and showed the characteristic age distribution expected. GP questionnaires were received for 4634 of 4900 cohort patients (95% response rate), and psoriasis diagnoses were confirmed in 90% of patients. Duration of disease in the database showed substantial agreement with physician query (κ = 0·69). GPs confirmed that the psoriasis diagnosis was corroborated by a dermatologist in 91% of patients whose database records contained a dermatology referral code associated with a psoriasis code. We achieved good discrimination between patients with and without extensive disease based on the number of psoriasis codes received per year (area under curve = 0·8). CONCLUSIONS: THIN is a valid data resource for studying psoriasis and can be used to identify characteristics of the disease such as duration and confirmation by a dermatologist.

Cause-specific mortality in patients with severe psoriasis: a population-based cohort study in the U.K.

BACKGROUND: Severe psoriasis is associated with excess mortality and increased risk of cardiovascular death. Population-based data evaluating cause-specific mortality in patients with psoriasis are limited. OBJECTIVES: To describe cause-specific mortality in patients with severe psoriasis. METHODS: We performed a cohort study from 1987 to 2002 of patients ≥18 years using the General Practice Research Database. We compared patients with a psoriasis code and a history of systemic therapy consistent with severe psoriasis (n=3603) with patients with no history of psoriasis (n=14,330). Age- and sex-adjusted Cox models were created for each of the leading causes of death defined by the Centers for Disease Control. RESULTS: Patients with severe psoriasis were at increased risk of death from cardiovascular disease [hazard ratio (HR) 1·57, 95% confidence interval (CI) 1·26-1·96], malignancies (HR 1·41, 95% CI 1·07-1·86), chronic lower respiratory disease (HR 2·08, 95% CI 1·24-3·48), diabetes (HR 2·86, 95% CI 1·08-7·59), dementia (HR 3·64, 95% CI 1·36-9·72), infection (HR 1·65, 95% CI 1·26-2·18), kidney disease (HR 4·37, 95% CI 2·24-8·53) and unknown/missing causes (HR 1·43, 95% CI 1·09-1·89). The absolute and excess risk of death was highest for cardiovascular disease (61·9 and 3·5 deaths per 1000 patient-years, respectively). CONCLUSIONS: Severe psoriasis is associated with an increased risk of death from a variety of causes, with cardiovascular death being the most common aetiology. These patients were also at increased risk of death from causes not previously reported, such as infection, kidney disease and dementia. Additional studies are necessary to determine the degree to which excess causes of death are due to psoriasis, its treatments, associated behaviours, or other factors.

Reliability, validity and responsiveness to change of the Patient Report of Extent of Psoriasis Involvement (PREPI) for measuring body surface area affected by psoriasis.

BACKGROUND: The development of a simple, reliable, valid and responsive method for measuring the extent of skin involvement in psoriasis is important for use in epidemiological studies. OBJECTIVES: We sought to investigate the psychometric characteristics of the Patient Report of Extent of Psoriasis Involvement (PREPI), a single-question method for measuring body surface area affected by psoriasis. METHODS: This was a cross-sectional study of 140 patients with psoriasis, with an exploratory prospective longitudinal cohort component. Reliability was measured via a test-retest approach and criterion validity was investigated by comparing the PREPI with an assessment of body surface area of involvement by a dermatologist. We additionally compared Skindex-29 scores with the PREPI. To demonstrate responsiveness and establish a minimally important difference in the PREPI, we created receiver operating characteristic curves for the PREPI instrument. RESULTS: The test-retest reliability of the PREPI was nearly perfect [intraclass correlation coefficient (ICC) = 0.99, 95% confidence interval (CI) 0.97-0.99], and there was substantial agreement between patient and physician assessments (ICC = 0.82, 95% CI 0.75-0.87). The PREPI showed significant correlations with all Skindex-29 domains. We found the PREPI to be responsive to change and identified changes in the PREPI score that have good discrimination between patients with and without a minimally important clinical difference. CONCLUSIONS: Our study suggests that the PREPI is a reliable, valid and responsive measure of body surface area affected by psoriasis that may be useful for future epidemiological research.

Capecitabine/cisplatin versus 5-fluorouracil/cisplatin as first-line therapy in patients with advanced gastric cancer: a randomised phase III noninferiority trial.

BACKGROUND: To compare capecitabine/cisplatin with 5-fluorouracil/cisplatin as first-line treatment for advanced gastric cancer (AGC). PATIENTS AND METHODS: In this randomised, open-label, phase III study, patients received cisplatin (80 mg/m(2) i.v. day 1) plus oral capecitabine (1000 mg/m(2) b.i.d., days 1-14) (XP) or 5-FU (800 mg/m(2)/day by continuous infusion, days 1-5) (FP) every 3 weeks. The primary end point was to confirm noninferiority of XP versus FP for progression-free survival (PFS). RESULTS: A total of 316 patients were randomised to XP (n = 160) or FP (n = 156). In the per-protocol population, median PFS for XP (n = 139) versus FP (n = 137) was 5.6 versus 5.0 months. The primary end point was met with an unadjusted hazard ratio (HR) of 0.81 [95% confidence interval (CI) 0.63-1.04, P < 0.001 versus noninferiority margin of 1.25]. Median overall survival was 10.5 versus 9.3 months for XP versus FP (unadjusted HR = 0.85, 95% CI 0.64-1.13, P = 0.008 versus noninferiority margin of 1.25). The most common treatment-related grade 3/4 adverse events in XP versus FP patients were as follows: neutropenia (16% versus 19%), vomiting (7% versus 8%), and stomatitis (2% versus 6%). CONCLUSIONS: XP showed significant noninferiority for PFS versus FP in the first-line treatment of AGC. XP can be considered an effective alternative to FP.

A randomised multicentre phase II trial of capecitabine vs S-1 as first-line treatment in elderly patients with metastatic or recurrent unresectable gastric cancer.

This randomised multicentre phase II study was conducted to investigate the activity and safety of two oral fluoropyrimidines, capecitabine or S-1, in elderly patients with advanced gastric cancer (AGC). Elderly (>or=65 years) chemo-naive patients with AGC were randomly assigned to receive capecitabine 1250 mg m(-2) two times daily on days 1-14 every 3 weeks or S-1 40-60 mg two times daily according to body surface area on days 1-28 every 6 weeks. Ninety-six patients were enrolled and 91 patients were randomised to capecitabine (N=46) or S-1 (N=45). Overall response rate, the primary end point, was 27.2% (95% CI, 14.1-40.4, 12 of 44 assessable patients) with capecitabine and 28.9% (95% CI, 15.6-42.1, 13 of 45) with S-1. Median times to progression and overall survival in the capecitabine arm (4.7 and 9.5 months, respectively) were similar to those in the S-1 arm (4.2 and 8.2 months, respectively). The incidence of grade 3-4 granulocytopenia was 6.8% with capecitabine and 4.8% with S-1. Grade 3-4 nonhaematologic toxicities were: asthenia (9.1% with capecitabine vs 7.1% with S-1), anorexia (6.8 vs 9.5%), diarrhoea (2.3 vs 0%), and hand-foot syndrome (6.8 vs 0%). Both capecitabine and S-1 monotherapies were active and tolerable as first-line treatment for elderly patients with AGC.

Randomized phase II study of irinotecan, leucovorin and 5-fluorouracil (ILF) versus cisplatin plus ILF (PILF) combination chemotherapy for advanced gastric cancer.

BACKGROUND: Irinotecan, in combination with 5-fluorouracil (5-FU) or cisplatin, has demonstrated efficacy against advanced gastric cancer (AGC). PATIENTS AND METHODS: Chemotherapy-naive AGC patients were randomly assigned to receive irinotecan 150 mg/m(2) on day 1, leucovorin 20 mg/m(2) and a 22-h infusion of 5-FU 1000 mg/m(2) on days 1 and 2 (ILF) or ILF plus cisplatin 30 mg/m(2) on day 2 (PILF). Treatment was repeated every 2 weeks. RESULTS: Of 91 registered patients, 45 patients were treated with ILF and 45 with PILF. For both arms, 687 chemotherapy cycles were delivered (median = 7 for ILF and 8 for PILF). Both ILF and PILF were generally well tolerated and there was no relevant difference in the occurrence of overall grade 3/4 toxic effects between the two arms. Four patients died during treatment: one in the ILF and three in the PILF arm. The objective response rate was 42% for both arms. There was no significant difference in therapeutic efficacy between ILF and PILF with respect to progression-free survival (4.8 versus 6.2 months; P = 0.523) and overall survival (10.7 versus 10.5 months; P = 0.850). CONCLUSION: Both ILF and PILF are active as first-line chemotherapy for AGC. The addition of cisplatin, however, has no clear advantage over ILF.

The Global Precipitation Climatology Project (GPCP) Monthly Analysis (New Version 2.3) and a Review of 2017 Global Precipitation.

The new Version 2.3 of the GPCP Monthly analysis is described in terms of changes made to improve the homogeneity of the product, especially after 2002. These changes include corrections to cross calibration of satellite data inputs and updates to the gauge analysis. Over ocean, changes starting in 2003 result in an overall precipitation increase of 1.8% after 2009. Updating the gauge analysis to its final, high quality version increases the global land total by 1.8% for the post-2002 period. These changes correct a small, incorrect dip in the estimated global precipitation over the last decade in the earlier Version 2.2. The GPCP analysis is also used to describe global precipitation for 2017. The general La Nina pattern for 2017 is noted and the evolution from the early 2016 El Nino pattern is described. The 2017 global value is one of the highest for the 19792017 period, exceeded only by 2016 and 1998 (both El Nino years) and reinforces the small positive trend. Results for 2017 also reinforce significant trends in precipitation intensity (on a monthly scale) in the tropics. These results for 2017 indicate the value of the GPCP analysis for climate monitoring in addition to research.

The impact of multidisciplinary nutritional team involvement on nutritional care and outcomes in a medical intensive care unit.

The aim of this study was to evaluate nutritional care and outcomes in a medical intensive care unit (ICU) following multidisciplinary nutritional team (MNT) involvement. The authors retrospectively reviewed the data of all patients admitted to a medical ICU from April to October 2013 (pre-MNT period) and from April to October 2014 (post-MNT period). In total, 140 patients were included and allocated to the pre-MNT group (n=70) or the post-MNT group (n=70). The post-MNT group was more likely to use enteral nutrition (61.4 vs 37.1%, P=0.002). In terms of total calories and protein provided, the number of nutritional goal-achieved days during stays in ICU was significantly greater in the post-MNT group than in the pre-MNT group (63.7% vs 47.6%, P<0.05 and 44.3% vs 29.9%, respectively, P<0.05). The MNT activities resulted in significant improvements in terms of nutritional provision and adequacy in a medical ICU.

Metastasectomy for recurrent or metastatic biliary tract cancers: A single center experience.

PURPOSE: To assess efficacy or long-term result of metastasectomy for recurrent or metastatic biliary tract carcinoma (BTC), we conducted a retrospective review of the outcomes of metastasectomy for recurrent or metastatic BTCs, comprising intrahepatic cholangiocellular carcinoma (IHCCC), proximal and distal common bile duct cancer (pCBDC and dCBDC), gallbladder cancer (GBC), and ampulla of Vater cancer (AoVC). PATIENTS AND METHODS: The clinicopathological features and outcomes of BTC patients who underwent surgical resection for the primary and metastatic disease at the Gachon University Gil Medical Centre from 2003 to 2013 were reviewed retrospectively. RESULTS: We found 19 eligible patients. Primary sites were GBC (seven patients, 37%), IHCCC (five patients, 26%), dCBDC (three patients, 16%), pCBDC (two patients, 11%), and AoVC (two patients, 11%). Eight patients (42%) had synchronous metastasis whereas 11 (58%) had metachronous metastasis. The most common metastatic site was liver (nine patients, 47%), lymph node (nine patients, 47%), and peritoneum (three patients, 16%). Nine patients (47%) achieved R0 resection, whereas four (21%) and six (32%) patients had R1 and R2 resection, respectively. With a median follow-up period of 26.7 months, the estimated median overall survival (OS) was 18.2 months (95% confidence interval, 13.6-22.9 months). Lower Eastern Cooperative Oncology Group performance status (P = 0.023), metachronous metastasis (P = 0.04), absence of lymph node metastasis (P = 0.009), lower numbers of metastatic organs (P < 0.001), normal postoperative CA19-9 level (P = 0.034), and time from diagnosis to metastasectomy more than 1 year (P = 0.019) were identified as prognostic factors for a longer OS after metastasectomy. CONCLUSIONS: For recurrent or metastatic BTCs, metastasectomy can be a viable option for selected patients.

The extent of N epsilon-(carboxymethyl)lysine formation in lens proteins and polylysine by the autoxidation products of ascorbic acid.

The autoxidation of ascorbic acid (ASA) leads to the formation of compounds which are capable of glycating and crosslinking proteins in vitro. When the soluble crystallins from bovine lens were incubated with ASA in the presence of sodium cyanoborohydride, a single major adduct was observed, whose appearance correlated with the loss of lysine. When polylysine was reacted with equivalent amounts of ASA under the same conditions, this product represented half of the total lysine content after four weeks of incubation at 37 degrees C. This adduct was isolated and identified as N epsilon-(carboxymethyl)lysine (CML) by TLC, GC/MS and amino acid analysis. Several oxidation products of ASA were each reacted with polylysine in the presence of sodium cyanoborohydride to identify the reactive species. CML was the major adduct formed with either ASA and dehydroascorbic acid (DHA). Markedly diminished amounts were seen with L-2,3-diketogulonic acid (DKG), and L-threose, while no CML was formed with L-threo-pentos-2-ulose (L-xylosone). In the absence of sodium cyanoborohydride the yield of CML was similar with each of the ASA autoxidation products and required oxygen. Reactions with [1-14C]ASA gave rise to [14C]CML, but only with NaCNBH3 present. At least two routes of CML formation appear to be operating depending upon whether NaCNBH3 is present to reduce the putative Schiff base formed between lysine and DHA.

Intrarenal pseudoaneurysms complicating renal choriocarcinoma metastases: treatment with coil embolization.

Most intrarenal pseudoaneurysms result from a laceration of the renal artery or its branches. However, tumor-induced renal pseudoaneurysm is very rare. We report a case in which embolization of an intrarenal pseudoaneurysm complicating renal metastases resulting from a choriocarcinoma was successful.

Ramosetron for the prevention of cisplatin-induced acute emesis: a prospective randomized comparison with granisetron.

Control of nausea and vomiting is very important in determining patient compliance with cisplatin chemotherapy. A multicentre, randomized, single-blind study was conducted to compare the tolerability and efficacy of ramosetron with those of granisetron over 24 h following cisplatin administration to cancer patients. In eight study centres, a total of 194 adult patients were randomly assigned to receive either intravenous ramosetron 0.3 mg or intravenous granisetron 3.0 mg. The anti-emetic effect of ramosetron determined from the no-vomiting rate lasted longer, but there was no significant difference in the number of acute vomiting episodes or the severity of nausea between the two groups. In the tolerability evaluation, there were no statistically significant differences between the two groups, except for a higher incidence of dull headache in the granisetron group. Ramosetron and granisetron appear to have equivalent efficacy and tolerability profiles, but the effects of ramosetron on the prevention of acute vomiting in patients undergoing cisplatin chemotherapy were longer lasting.