Cadmium-induced renal dysfunction and mortality in two cohorts: disappearance of the association in a generation born later

The association between exposure to environmental cadmium and mortality was investigated in two cohorts. The study population consisted of 275 (cohort I) and 329 (cohort II) residents (aged >or=40 years) in a cadmium-polluted area, Nagasaki Prefecture, Japan, who had participated in health surveys conducted in 1982 and 1992, respectively. The follow-up period extended from 1982 or 1992 to 2005. In the study area, the dietary cadmium intake had decreased after 1980-1983 because of the restoration of cadmium-polluted paddy fields. In cohort I, the mortality rate among those with urinary beta2-microglobulin (beta2-MG) concentration >or=1000 microg/g creatinine (cr.) was 1.41 times higher than the regional reference rate (95% confidence interval [CI] 1.07-1.83). After adjusting for age and other variables, in men, urinary N-acetyl-beta-D-glucosaminidase, and in women, serum creatinine, beta2-MG clearance, and urinary beta2-MG were significantly associated with increased mortality. However, in cohort II, urinary beta2-MG or total protein was not significantly associated with survival. These findings indicate that cadmium-induced renal dysfunction was a significant predictor of mortality, but that such an association is disappearing, probably because of the selective loss of advanced cases and reduced exposure and body burden.     

All‐cause mortality increased by environmental cadmium exposure in the Japanese general population in cadmium non‐polluted areas

The aim of the present study was to evaluate the effect of environmental cadmium (Cd) exposure indicated by urinary Cd on all‐cause mortality in the Japanese general population. A 19‐year cohort study was conducted in 1067 men and 1590 women aged 50 years or older who lived in three cadmium non‐polluted areas in Japan. The subjects were divided into four quartiles based on creatinine adjusted U‐Cd (µg g^?1 cre). The hazard ratio (HR) and 95% confidence interval (CI) for continuous U‐Cd or the quartiles of U‐Cd were estimated for all‐cause mortality using a proportional hazards regression.The all‐cause mortality rates per 1000 person years were 31.2 and 15.1 in men and women, respectively. Continuous U‐Cd (+1 µg g^?1 cre) was significantly related to the all‐cause mortality in men (HR 1.05, 95% CI: 1.02–1.09) and women (HR 1.04, 95% CI: 1.01–1.07). Furthermore in men, the third (1.96–3.22 µg g^?1 cre) and fourth quartile (≥3.23 µg g^?1 cre) of U‐Cd showed a significant, positive HR (third: HR 1.35, 95% CI: 1.03–1.77, fourth: HR 1.64, 95% CI: 1.26–2.14) for all‐cause mortality compared with the first quartile (<1.14 µg g^?1 cre). In women, the fourth quartile of U‐Cd (≥4.66 µg g^?1 cre) also showed a significant HR (1.49, 95% CI 1.11–2.00) for all‐cause mortality compared with the first quartile (<1.46 µg g^?1 cre).In the present study, U‐Cd was significantly associated with increased mortality in the Japanese general population, indicating that environmental Cd exposure adversely affects the life prognosis in Cd non‐polluted areas in Japan. Copyright © 2014 John Wiley & Sons, Ltd.     

Differences on the prevalence of cervical HPV between Lithuania and Belarus

In some countries the cervical cancer incidence and mortality rates are much higher compared to the European average. The differences of HPV and its type prevalence between countries and regions influence cervical cancer incidence and mortality. Regarding the differences in cervical cancer incidence and mortality in Lithuania and Belarus, the aim of this study was to describe HPV infection level and HPVs type distribution among two study groups of patients with moderate or severe cervical intraepithelial neoplasia (CIN2-3) and cervical cancer. Our data shows that 74.2% [95% CI: 63.64÷84.76] of Lithuanian patients with cervical cancer and 85.6% [95% CI: 85.53÷92.85] of the study group with CIN2-3 were HPV positive, while in the study groups of Belarusian patients HPV infection was detected in 92.6% [95% CI, 74.25÷98.71] and 65.4% [95% CI, 44.36÷82.06] cases respectively. HPV 16 was the most prevalent type in Lithuanian as well as in Belarusian patients of the study groups. HPV 18 in Lithuanian patients of the study group with cervical cancer was identified in 10.2% [95% CI: 1.73÷18.67] and in the study group with CIN2-3 — in 2.6% [95% CI: 0.95÷6.15] of cases. HPV 18 was not detected in Belarusian patients of both groups.     

N-Acetyltransferase 2 and glutathione s-transferase M1 in colon and rectal cancer cases from an industrialized area

Apart from genetics, nutrition, and environment, occupational factors also play an important role in colon and rectal cancer development. The aim of this study was to examine these cancer types in an area of former coal, iron, and steel industries, which was found to display an increased incidence of colon cancer mortality. N-Acetyltransferase 2 (NAT2) and glutathione S-transferase M1 (GSTM1) genotypes were investigated in 108 colon cancer cases, 80 rectum cancer cases, and 188 controls (suffering from nonmalignant diseases). Further, in a pilot study, 28 colorectal cancer patients were NAT2 phenotyped by the caffeine test. Possible occupational and nonoccupational risk factors were investigated by a personal interview. The frequency of rapid NAT2 genotype was 35% in colon cancer cases, 47% in rectal cancer cases, and 42% in controls (GSTM1 0/0 genotype: 53, 46, and 47%, respectively). In the 29 patients with cancer in the ascending colon, 10% were of the rapid NAT2 genotype. In the pilot study the frequency of the rapid NAT2 phenotype was 49%. The only major professional group with an elevated risk was painters (colon cancer OR 2.48, 95% CI 0.4-15.23; rectal cancer OR 5.65, 95% CI 1.06-30.21). In contrast to early studies, in the present study the slow NAT2 status is overrepresented. As colorectal cancer is associated with nutrition and physical activity, present findings may be due to excessive physical heavy work and the resulting nutrition in this area.     

Meta-analysis: cancer risk of low-grade dysplasia in chronic ulcerative colitis

BACKGROUND: The cancer risk of low-grade dysplasia (LGD) in chronic ulcerative colitis is variable and its management remain contentious. AIM: To determine the risk of cancer or any advanced lesion once LGD is diagnosed. METHODS: A MEDLINE, EMBASE and Pub Med search was conducted using the key words 'surveillance', 'colorectal cancer', 'low-grade dysplasia' and 'ulcerative colitis'. A random effects model of meta-analysis was used. RESULTS: Twenty surveillance studies had 508 flat LGD or LGD with dysplasia-associated lesion or mass. An average of 4.3 colonoscopies was performed/patient post-LGD diagnosis (range: 3-7.6). An average of 18 biopsies taken per colonoscopy (range: 9-24) detected 73 advanced lesions (cancer or high-grade dysplasia) pre-operatively. The cancer incidence was 14 of 1000 (95% CI: 5.0-34) person years duration (pyd) and the incidence of any advanced lesion was 30 of 1000 pyd (95% CI: 12-76). When LGD is detected on surveillance there is a ninefold risk of developing cancer (OR: 9.0, 95% CI: 4.0-20.5) and 12-fold risk of developing any advanced lesion (OR: 11.9, 95% CI: 5.2-27). CONCLUSIONS: The risk of developing cancer in patients with LGD is high. These estimates are valuable for decision-making when LGD is encountered on surveillance.     

Exposure-toxicity relationships for tipifarnib in cancer patients

AIMS: To explore the potential relationship between systemic exposure to tipifarnib and the incidence of toxicity in cancer patients. METHODS: Data from 673 subjects (540 receiving tipifarnib and 133 receiving placebo) were included in the analysis. Tipifarnib was administered in doses ranging from 100 mg to 850 mg twice daily under fed conditions for 21 days in a 28 day cycle. Univariate and multivariate logistic regression models were used to evaluate the relationships between tipifarnib exposure and haematological (neutropenia and thrombocytopenia) and nonhaematological toxicities. Tipifarnib exposure was quantified as the area under the curve during the first cycle of chemotherapy (AUC), the maximum plasma concentration (C(max)), the time above plasma tipifarnib concentrations of 400 (T400) and 600 ng ml(-1) (T600), the cumulative area under the curve (AUC(T)), and the area under the curve density (AUC(D)), defined as the ratio AUC(T) to the duration of treatment. The nonhaematological toxicities measured were elevation of AST, ALT, bilirubin and serum creatinine, the occurrence of a skin rash, CNS or peripheral neuropathy, nausea and vomiting, diarrhoea and inflammation of the gastrointestinal tract. Odds ratios (OR) associated with drug exposure were used to measure the effect of the drug. RESULTS: Tipifarnib AUC exhibited a positive and significant association with neutropenia grade > or =3 (OR 1.69, 95% CI 1.47, 1.95) and thrombocytopenia grade > or =3 (OR 1.41, 95% CI 1.21, 1.63) in patients with solid tumours, but not in refractory or relapsed AML patients. The incidence of exposure-related nonhaematological toxicity is small regardless of tumour type. No association was found between tipifarnib AUC and the elevation of AST, ALT and total bilirubin, and nausea and vomiting. There was a weak relationship between tipifarnib AUC and serum creatinine elevation (OR 1.18, 95% CI 1.11, 1.26), CNS (OR 1.05, 95% CI 1.01, 1.10) and peripheral neurotoxicity (OR 1.10, 95% CI 1.03, 1.18), diarrhoea (OR 1.14, 95% CI 1.08, 1.21), gastrointestinal tract inflammation (OR 1.13, 95% CI 1.07, 1.19), and skin rash (OR 1.10, 95% CI 1.04, 1.17). CONCLUSIONS: In those patients who develop severe toxicity, dose reduction may improve the tolerability of tipifarnib. However, an exposure-guided approach to dosage adjustment to limit haematological and nonhaematological toxicity is not warranted.     

肠内与肠外营养对胃癌手术后患者的临床影响——中文文献Meta分析

目的：评价胃癌术后对患者进行肠内／肠外营养治疗的过程中病人并发症的发生率、术后胃肠功能恢复时间以及平均住院天数。方法：检索中国期刊全文数据库,筛选有关对照临床试验．采用RevMan4.1进行Meta分析。结果：纳入12篇研究．胃癌术后肠内营养（EN）与肠外营养（PN）相比．并发症的发生率的比值比（OR）为053．95％CI[0.35．079],P=0．002：胃肠道功能恢复时间的加权均数差值（WMD）为-2654,95％CI[-366,-16．48】．P〈0．00001：住院时间的加权均数差值（WMD）为-406,95％CI[-715,-097],P=0．01〈O05。结论：进行胃癌手术后的患者．采用肠内营养时并发症的发生率较低．术后胃肠功能恢复较快,住院天数较短。     

Meta-analysis of the clinical efficacy and safety of oxycodone and morphine in cancer pain treatment

In the present study, the efficacy and safety of oxycodone and morphine in the treatment of cancer pain were compared in a meta-analysis with the goal of providing a reference for drug selection in clinical practice. Electronic literature databases were searched for articles published through February 2015, including PubMed, MEDLINE, the Cochrane library, and Embase; and the China National Knowledge Internet, VIP Databases and Wanfang Databases for studies published in Chinese. Only randomized controlled trials were selected. The primary outcome measures were efficacy and the incidence of adverse drug reactions (ADRs). Data were extracted from the studies by two independent reviewers. A total of 15 studies containing 1338 patients were included in the analysis. The studies were divided into two subgroups according to different scoring methods. The pain relief efficacies of oxycodone and morphine were rated by the numerical rating scale (NRS) (risk ratio [RR]: 1.04; 95% confidence interval [CI]: 0.97–1.11). Others were rated by the visual analog scale (VAS) (RR: 1.03; 95% CI: 0.97–1.10). Five studies showed that pain intensity scores did notsignificantly differ between oxycodone and morphine treatments (standard mean difference [SMD] = 0.16, 95% CI: –0.01~0.33, P = 0.06). Regarding ADRs, the incidence of constipation was lower in the oxycodone group (RR: 0.70; 95% CI: 0.58–0.85). No statistical difference was observed among other ADRs. The efficacies of oxycodone and morphine were similar in treating cancer pain. However, the incidence of constipation was lower in patients treated with oxycodone.     

A 30-year mortality and respiratory morbidity study of refractory ceramic fiber workers

Aim: Report mortality (n?=?1119), cancer incidence (n?=?1207) and radiographic (n?=?1451) findings from a 30-year investigation of current and former refractory ceramic fiber (RCF) workers.

Methods: Cause of death, health and work histories, radiographs and spirometry were collected. Mortality and cancer incidence were analyzed. Logistic regression analysis investigated the associations of latency and cumulative fiber exposure (CFE) on radiographic changes.

Results: The mortality study showed no increase in standardized mortality rates (SMR) for lung cancer, but urinary cancers were significantly elevated in the higher exposed group (SMR?=?3.62, 95% CI: 1.33–7.88) and leukemia in the total cohort (SMR?=?2.51, 95% CI: 1.08–4.94). One death attributed to mesothelioma was identified (SMR?=?2.86, 95% CI: 0.07–15.93) in a worker reporting some asbestos exposure. The overall rate of pleural changes was 6.1%, attaining 21.4% in the highest CFE category for all subjects (adjusted odds ratio (aOR)?=?6.9, 95% CI: 3.6–13.4), and 13.0% for those with no reported asbestos exposure (OR=?9.1, 95% CI: 2.5–33.6). Prevalence for recent hires (≥1985) was similar to the background. Interstitial changes were not elevated. Localized pleural thickening was associated with small decreases in spirometry results.

Conclusion: Increases in leukemia and urinary cancer but not lung cancer mortality were found. One death attributed to mesothelioma was observed in a worker with self-reported asbestos exposure and a work history where occupational asbestos exposure may have occurred, rendering uncertainties in assigning causation. Radiographic analyses indicated RCF exposure alone is associated with increased pleural but not interstitial changes. Reductions in RCF exposure should continue. The mortality study is ongoing.     

Urinary alpha 1-microglobulin as an indicator protein of renal tubular dysfunction caused by environmental cadmium exposure

An epidemiologic investigation was carried out to clarify the significance of the urinary excretion of alpha 1-microglobulin (alpha 1-MG) in people aged 50 years and over living in a Cd-polluted area in Japan. Approximately 80% of the population participated in the health examination. The urinary and serum levels and the relative clearance of alpha 1-MG to creatinine clearance were compared with various parameters (age, urinary beta 2-microglobulin (beta 2-MG), total protein, Cd, Cu and Zn, serum beta 2-MG, creatinine and blood urea nitrogen and relative clearances of alpha 1-MG, beta 2-MG, inorganic phosphate and uric acid). It was found that the urinary excretion of alpha 1-MG is closely associated with the urinary Cd and Cu and with the indices of renal dysfunction listed above. These results suggest that the urinary alpha 1-MG level markedly reflects a degree of proximal tubular dysfunction and that it may be useful as one of the screening measures for proximal tubular dysfunction caused by environmental Cd exposure.     

Renal and hepatic accumulation of cadmium and lead in the expression of CYP4F2 and CYP2E1

The present study examined accumulation of the metal toxins cadmium (Cd) and lead (Pb) in relation to the abundance of cytochrome P450 4F2 (CYP4F2), CYP2E1 and concentrations of zinc and copper in liver and kidney samples using immunoblotting coupled with metal analysis. The post mortem liver and kidney cortex samples were from 23 males and 8 females aged 3-89 years. All were Caucasians who had not been exposed to metals in the workplace. Average kidney cortex Cd load of 17.4 microg/g w.w. was 17 times greater than average liver Cd load (1.1 microg/g w.w.). In contrast, average kidney cortex Pb load of 0.09 microg/g w.w. was two times lower than liver Pb load of 0.19 microg/g w.w. Average Zn and Cu concentrations in the kidney cortex samples were 67% and 33% lower than those in the liver. Liver and kidney Cd loads, but not liver or kidney Pb loads, correlated positively with donors' age. After controlling for liver Cd load, an inverse correlation was seen between Zn and age (partial r=-0.39, P=0.02), suggesting reduction in liver Zn levels in old age. Liver CYP2E1 protein abundance correlated with age-adjusted Cd load (partial r=0.37, P=0.02) whereas kidney CYP4F2 protein abundance showed a positive correlation with age-adjusted Cd loads (partial r=0.40, P=0.02). These findings suggest that Cd may be an inducer of renal CYP4F2 and hepatic CYP2E1 and that increased renal CYP4F2 expression may implicate in Cd-linked renal tubular dysfunction and high blood pressure, involving CYP4F2-dependent arachidonic acid metabolism.     

Metabolic coronary-flow regulation and exogenous nitric oxide in human coronary artery disease: assessment by intravenous administration of nitroglycerin

We sought to evaluate the effect of intravenous administration of the nitric oxide--donor substance nitroglycerin (NTG) on metabolic coronary-flow regulation in patients with coronary artery disease (CAD). In 12 patients with stable CAD, we measured coronary sinus blood flow and myocardial oxygen supply and consumption (MVO2) at sinus rhythm and during atrial pacing (30 beats/min above sinus rate), both at control and during infusion of NTG, 1 microg/kg/min, and NTG, 2 microg/kg/min. To study metabolic coronary vasodilation, changes in myocardial oxygen supply were related to pacing-induced changes in MVO2, by using standard regression analysis. The myocardial oxygen supply/consumption ratio (i.e., the slope of the regression line at control, characterizing physiological metabolic coronary flow regulation) was compared with the ratios obtained during infusion of NTG. Compared with control measurements, NTG, 1 microg/kg/min, and NTG, 2 microg/kg/min, attenuated pacing-induced increases in MVO2 by 29 and 60%, respectively, whereas coronary blood flow during pacing remained unchanged. At control, normal metabolic coronary-flow regulation resulted in a myocardial oxygen supply/demand ratio of 1.39 (95% CI, 1.29-1.49). This ratio did not change during NTG, 1 microg/kg/min: 1.44 (95% CI, 1.33-1.56). However, during NTG, 2 microg/kg/min, this ratio significantly increased to 1.84 (95% CI, 1.63-2.05; p<0.01). Intravenous administration of high-dose NTG, a donor of exogenous NO, blunts pacing-induced increases in MVO2 and may increase metabolic coronary vasodilation in patients with CAD.     

Addition of vandetanib to chemotherapy in advanced solid cancers: a meta-analysis

The addition of vandetanib to chemotherapy has been shown to have a marked effect on patients with advanced cancers who had failed previous chemotherapy. We carried out a meta-analysis to determine the efficacy and safety of vandetanib compared with chemotherapy in patients with advanced cancers. For this meta-analysis, we selected randomized clinical trials that compared vandetanib-based therapy (VBT) with the matched chemotherapy or placebo alone in patients with advanced cancers. The outcomes included overall survival (OS), progression-free survival (PFS), the objective response rate, and toxicities. Hazard ratios (HRs) and odds ratios were reported with 95% confidence intervals (CIs). A total of 14 eligible trials were included for the meta-analysis, with 2995 patients in the VBT group and 2479 patients in the control group. A significant improvement was observed in PFS (HR 0.76, 95% CI 0.68-0.86 in all cancers, HR 0.80, 95% CI 0.70-0.90 in lung cancer, HR 0.54, 95% CI 0.40-0.74 in thyroid cancer) and in objective response rate (odds ratio 2.09, 95% CI 1.42-3.07) in the VBT group. However, no significant difference was found in OS (HR 0.96, 95% CI 0.90-1.03). The subgroups of patients with non-small-cell lung cancer who benefited from vandetanib therapy were identified as those with a history of smoking (HR 0.87, 95% CI 0.80-0.95) and an adenocarcinoma histology (HR 0.85, 95% CI 0.77-0.94). In addition, patients who received VBT had an increased incidence of adverse events such as rash, diarrhea, and neutropenia. The addition of vandetanib to chemotherapy significantly improves PFS in patients with locally advanced or metastatic cancers, especially lung and thyroid cancer.     

Declining incidence of peptic ulcer but not of its complications: a nation-wide study in The Netherlands

BACKGROUND: Despite reports of decreasing hospitalizations and mortality due to peptic ulcer, it is unclear whether the incidence has truly declined over time. AIM: To investigate time trends in the incidence of and in hospital admission rates for peptic ulcer in the Netherlands. METHODS: The nationwide registry of pathology reports (PALGA) and the national registry of hospital admissions (Landelijke Medische Registratie) were used. Standardized morbidity ratios were calculated to assess the magnitude of the changes. RESULTS: The age-adjusted incidence of gastric ulcer halved for both men (standardized morbidity ratio 0.48; CI 0.46-0.49) and women (standardized morbidity ratio 0.49; CI 0.47-0.51). Although the number of gastric biopsies obtained at endoscopy increased, the proportion with a diagnosis of peptic ulcer decreased by more than 50% (standardized morbidity ratio 0.47; CI 0.46-0.49). The admission rate for peptic ulcer more than halved between 1980 and 2003. In contrast, admission rates for complicated ulcers barely changed and slightly increased among women. CONCLUSIONS: The incidence of histopathologically confirmed gastric ulcer halved between 1992 and 2003 in the Netherlands. As the number of gastric biopsies increased in this period, a true decrease is likely. Hospital admissions for peptic ulcer declined dramatically between 1980 and 2003, but remained unchanged or slightly increased for complicated ulcers.     

胃癌患者的大肠癌同步发生率研 究简

目的 研究胃癌患者的大肠癌同步发生情况.方法 选取164例胃癌患者和328例年龄及性别匹配的非胃癌患者进行分析.结果 大肠癌的发病率在胃癌组为32.93％,显著高于对照组的16.46％ （P ＜0.01）.大肠癌胃癌患者的比值比（OR）为3.11;95％置信区间（CI）为1.70 ～ 5.62.特别是大肠癌发病率的差异更加突出,在50岁以上的患者OR为3.53; 95％ CI为1.78 ～6.97.结论 胃癌患者大肠癌的同步患病率高于非胃癌患者,故胃癌患者应视为大肠癌的高危险群,应进行筛选推荐和大肠镜检查.     

Mortality and cancer incidence in New Zealand pulp and paper mill workers

AIMS: To evaluate mortality and cancer incidence in a cohort of workers employed in the New Zealand pulp and paper industry, and to identify the exposures responsible for any increased risk. METHODS: A total of 8456 workers employed for at least one year in three pulp and paper mills between 1978 and 1990 were followed up until 1992. The observed number of deaths and cancer cases was compared with expected numbers calculated using five-year age-specific rates for the New Zealand population. RESULTS: Vital status was determined for 81% of the cohort, and for 93% of the total person-years at risk. Mortality from all causes (standardised mortality ratios (SMR) = 0.80, 95% confidence intervals [CI] 0.71-0.89; 314 deaths), and from all malignant neoplasms (SMR = 0.95, 95% CI 0.78-1.15, 103 deaths), was lower than expected. Mortality from lung cancer (SMR = 1.33, 95% CI 0.94-1.83, 37 deaths) was marginally increased. CONCLUSIONS: No overall increase in mortality from cancer or other causes was observed in this cohort. A small increase in lung cancer risk is suggested, although this was not statistically significant. Numbers of cases were too small for detailed analyses of associations between disease and specific exposures.     

Dose–response for adrenal suppression with hydrofluoroalkane formulations of fluticasone propionate and beclomethasone dipropionate

AIMS: With the recent introduction of hydrofluoroalkane (HFA) inhalers it is important to know the relative systemic safety profiles of inhaled corticosteroids. We therefore decided to compare systemic bioavailability of HFA-beclomethasone dipropionate (BDP) vs HFA-fluticasone propionate (FP). METHODS: Sixteen healthy volunteers were randomised in placebo-controlled single blind cross-over fashion to receive 3 weeks with HFA-FP or HFA-BDP, given as 1 week cumulative doubling doses (nominal ex-valve) of 500, 1000 and 2000 microg day(-1), with a 1 week placebo run-in and wash-out. Overnight (22.00 h to 08.00 h) and early morning (08.00 h) urinary cortisol/creatinine excretion and 08.00 h serum cortisol were measured after each placebo and dosing period. All data were log-transformed to normalize their distribution. RESULTS: Urine and serum cortisol were suppressed by 2000 microg FP and BDP vs placebo and by 1000 microg BDP vs placebo for urinary cortisol/creatinine (P < 0.05). Overnight urinary cortisol/creatinine ratio (the primary endpoint) was suppressed more by 1000 microg BDP vs 1000 microg FP (P < 0.05), amounting to a geometric mean fold difference (95% CI) of 1.64 (1.04-2.56). There were also more individual low values less than 3 nmol mmol(-1) with BDP than FP at 1000 microg: n = 8/16 vs n = 2/16 (P < 0.05). CONCLUSIONS: There was dose-related suppression of corrected urinary cortisol/creatinine with the HFA formulations of BDP and FP. Suppression of overnight urinary cortisol/creatinine ratio was significantly greater with HFA-BDP than HFA-FP at 1000 microg. This suggests that the greater glucocorticoid potency of HFA-FP may be offset by the greater lung bioavailability of HFA-BDP.     

Serum cystatin C is not a better marker of creatinine or digoxin clearance than serum creatinine

AIMS: To assess whether cystatin C, a new serum marker of renal function, is a better index of creatinine or digoxin clearance than serum creatinine in older people. METHODS: Twenty-two volunteers over the age of 65 years (mean 73 +/- 5) were recruited from a healthy elderly volunteer database. None of the volunteers was taking digoxin or other medication known to interfere with digoxin kinetics or assay. Digoxin was infused at a dose of 7-10 microg kg(-1) and blood samples were taken over the following 48 h and assayed for serum digoxin. Serum cystatin C, creatinine and creatinine clearance were measured and a calculated creatinine clearance was estimated using the Cockcroft Gault formula. Digoxin clearance was calculated using a pharmacokinetic software package. All values were log transformed to normalize their distribution. RESULTS: Of the 22 volunteers enrolled into the study, 18 completed the study. Serum cystatin C ranged between 0.72 and 1.89 mg l(-1) and serum creatinine ranged from 69.6 to 153.9 micromol l(-1). Measured creatinine clearance ranged from 38 to 123 ml min(-1) and calculated creatinine clearance from 29.5 to 88.0 ml min(-1). Digoxin clearance ranged from 51.0 to 103.5 ml min(-1). Cystatin C correlated extremely well with creatinine (r=0.93, P<0.001, 95% CI 0.82, 0.97) and with creatinine clearance (r=0.67, P=0.002, 95% CI 0.3, 0.87). Neither serum cystatin C nor serum creatinine correlated with digoxin clearance (r=0.25, P=0.31, 95% CI -0.25, 0.64 and r=0.44, P=0.068, 95% CI -0.03, 0.75, respectively). Measured creatinine clearance, however, did correlate well with digoxin clearance (r=0.55, P=0.018, 95% CI 0.11, 0.81). CONCLUSIONS: Serum cystatin C and serum creatinine show very similar correlations with creatinine and digoxin clearances. Serum cystatin C does not offer any advantages in this respect. It remains to be seen whether cystatin C offers any advantage over creatinine in elderly people in other respects.     

No increase in risk of fracture, malignancy or mortality in dermatitis herpetiformis: a cohort study

Background  Dermatitis herpetiformis forms part of the same spectrum of gluten-sensitive disorders as coeliac disease yet may have different risks of morbidity and mortality.
Aims  To quantify the risks of fracture, malignancy and mortality in people with dermatitis herpetiformis compared with the general population.
Methods  Using the General Practice Research Database, we identified 846 people with dermatitis herpetiformis and 4225 age-, gender- and practice-matched controls. We used Cox regression to estimate hazard ratios.
Results  Comparing people with dermatitis herpetiformis to the general population, the overall hazard ratio for any fracture was 1.1 (95% CI: 0.77–1.52). The overall hazard ratio for any malignancy was 1.0 (95% CI: 0.73–1.49); there was no increased risk of gastrointestinal (HR: 1.6; 95% CI: 0.67–3.67) or lymphoproliferative cancers (HR: 1.6; 95% CI: 0.44–6.06). A reduction in risk of breast cancer was not statistically significant (HR: 0.19; 95% CI: 0.03–1.39). The hazard ratio for all-cause mortality was 0.93 (95% CI: 0.70–1.23).
Conclusions  Unlike the fivefold increase in risk seen in coeliac disease, we found no increased risk of lymphoproliferative cancer and no increase in fracture, malignancy or mortality in people with dermatitis herpetiformis compared with the general population. It is not clear whether differences in degree of intestinal inflammation or other reasons account for this. Like coeliac disease, dermatitis herpetiformis may protect against breast cancer.     

Estimation of benchmark dose for renal dysfunction in a cadmium non-polluted area in Japan

Previously, the association between urinary cadmium (Cd) concentration and indicators of renal dysfunction, including beta(2)-microglobulin (beta(2)-MG), total protein and N-acetyl-beta-D-glucosaminidase (NAG) were investigated in 1270 inhabitants > or = 50 years of age (547 men, 723 women) in a Cd non-polluted area in Japan and showed that a dose-response relationship existed between renal effects and Cd exposure in the general environment without any known Cd pollution. However, the threshold levels of urinary Cd could not be estimated at that time. In the present study, the threshold levels of urinary Cd were estimated as the benchmark dose low (BMDL) using the benchmark dose (BMD) approach. Urinary Cd excretion was divided into 6-7 categories, and an abnormality rate was calculated for each. Cut-off values for urinary substances were defined as corresponding to the 84% upper limit values, which were calculated from 2034 persons who had been living in the non-polluted areas and did not smoke. Then the BMD and BMDL were calculated using a log-logistic model. The values of BMD and BMDL for all urinary substances could be calculated. The BMDL for the 84% cut-off value of beta(2)-MG, setting an abnormal value at 5%, was 2.0 microg g(-1) creatinine (cr) in men and 1.6 microg g(-1) cr in women. In conclusion, the present study demonstrated that the threshold level of urinary Cd could be estimated in people living in the general environment without any known Cd-pollution in Japan, and the value was inferred to be almost the same as that in Belgium and Sweden.