Geographical variation in incidence of prostate cancer in Sweden

OBJECTIVE: To investigate the geographical variation in prostate cancer incidence in Sweden, in particular the incidences of screening-detected tumours and curative treatment of prostate cancer. MATERIAL AND METHODS: Data were retrieved from the National Prostate Cancer Register of Sweden for all cases of prostate cancer diagnosed in the year 2000-01. There were a total of 14 376 cases of prostate cancer and the mean total annual age-adjusted incidence was 197/100 000 men. There were 3318 cases in tumour category T1c, i.e. non-palpable tumours diagnosed during work-up for an elevated serum level of prostate-specific antigen, 1006 of which (30%) were asymptomatic and detected at a health check-up. RESULTS: The difference between the counties with the lowest and highest age-adjusted incidences per 100 000 men of total prostate cancer was almost twofold (128 vs 217). The corresponding variation in incidence of category T1c tumours was more than fourfold (13 vs 60); the difference in incidence of T1c tumours detected in asymptomatic men was up to 10-fold (2 vs 20); and there was more than a fourfold variation in incidence of curative treatment between counties (13 vs 67). Measured incidences were mostly highest in urban regions and in counties with university hospitals. CONCLUSION: There are large geographical variations in prostate cancer incidence and in the frequency of curative treatment for prostate cancer in Sweden and there appear to be large geographical variations in the uptake of prostate cancer screening.     

Prevalence of methylenetetrahydrofolate gene (MTHFR) C677T polymorphism among chronic hemodialysis patients and its association with cardiovascular disease: a cross-sectional analysis

Introduction  

Cardiovascular disease (CVD) remains the main cause of morbidity and mortality in end stage renal disease (ESDR) patients. A common C–T mutation at nucleotide position 677 (C677T) has been identified in the gene coding for methylenetetrahydrofolate reductase (MTHFR), which is involved in the remethylation of homocysteine (Hcy). The C677T mutation decreases MTHFR activity, tends to increase Hcy concentrations in individuals who are homozygous for the T/T genotype, and may predispose to CVD. Recent reports suggested that the T/T genotype may predispose type 2 diabetic and hypertensive patients to the development of progressive renal insufficiency. The aim of this cross-sectional study is to analyze the prevalence of the MTHFR C677T gene polymorphism among a group of chronic dialysis patients in comparison to age- and gender-matched controls. We also examined the possible association between CVD and MTHFR gene mutation in this group of patients.     

Recombinant human growth hormone treatment after liver transplantation in childhood: the 5-year outcome

BACKGROUND: Because the results of short-term recombinant human growth hormone (rhGH) treatment in children with growth impairment after liver transplantation (LTx) have been promising, we have studied the long-term effects of rhGH on growth and graft function after LTx. METHODS: Indications for rhGH treatment were height standard deviation score (hSDS) below -2.0 or growth velocity SDS below 0 and LTx at least 18 months before inclusion. Eight growth-retarded children were treated with rhGH for more than 5 years. RESULTS: During the first year, median growth rate improved from 3.3 to 7.0 cm/year. In the second and third year, growth velocity remained high at 6.6 cm/year and 6.2 cm/year, respectively (P=0.008). In the fourth year, median growth velocity started to decline but still remained above baseline during the fifth year of treatment (4.2 cm/year). The median hSDS improved from -3.6 to -2.7. During the rhGH treatment, no acute rejection episodes were detected, and graft function remained stable in all except one patient. She was diagnosed with chronic rejection in the third year of rhGH treatment. The patient had elevated liver enzymes and abnormal liver function tests already before rhGH treatment. CONCLUSIONS: The efficacy of rhGH treatment is sustained after the first year in liver-transplant children with non-GH-deficient growth retardation. Because of a potential risk of side effects, close monitoring of these patients is required.     

Risk of non-Hodgkin lymphoma and lymphoproliferative precursor diseases in US veterans with hepatitis C virus

Context  Hepatitis C virus (HCV) infection causes liver cancer and cirrhosis and may also increase the risk of other tumors, particularly hematopoietic malignancies and thyroid cancer. Previous studies have been too small to adequately assess these risks. Objective  To test the hypothesis that HCV infection is associated with increased risk for hematological malignancies, related lymphoproliferative disorders, and thyroid cancer. Design, Setting, and Patients  A retrospective cohort study of users of US Veterans Affairs health care facilities from 1997-2004, which included 146 394 patients infected with HCV who had at least 2 visits with a diagnostic code for HCV infection, and 572 293 patients uninfected with HCV. To assemble the HCV-uninfected cohort, we randomly selected up to 4 patients per patient infected with HCV from all veterans who matched on age, sex, and baseline visit date and type (inpatient or outpatient). Individuals with human immunodeficiency virus were excluded. Main Outcome Measures  Risks of hematopoietic malignancies, related lymphoproliferative precursor diseases, and thyroid cancer, adjusting for selection factors, race, era of military service, and use of medical services. Results  The mean (SD) age of the patients was 52 (8) years, and 97% were men. Risks for non-Hodgkin lymphoma (n = 1359), Waldenström macroglobulinemia (n = 165), and cryoglobulinemia (n = 551) were increased with HCV infection (adjusted hazard ratio [HR], 1.28; 95% confidence interval [CI], 1.12-1.45; adjusted HR, 2.76; 95% CI, 2.01-3.79; and adjusted HR, 3.98; 95% CI, 3.36-4.72; respectively). We found no significantly increased risk for other hematological malignancies. Although thyroiditis risk was slightly increased, risk for thyroid cancer (n = 320) was not (adjusted HR, 0.72; 95% CI, 0.52-0.99). Adjusted P values for non-Hodgkin lymphoma, Waldenström macroglobulinemia, cryoglobulinemia, and thyroiditis were all <.0038, the Bonferroni threshold for statistical significance considering multiple comparisons. Conclusions  Hepatitis C virus infection confers a 20% to 30% increased risk of non-Hodgkin lymphoma overall, and a 3-fold higher risk of Waldenström macroglobulinemia, a low-grade lymphoma. Risks were also increased for cryoglobulinemia. These results support an etiological role for HCV in causing lymphoproliferation and causing non-Hodgkin lymphoma.      

Protease inhibitors and cardiovascular outcomes in patients with HIV-1

Protease inhibitors for treatment of HIV-1 have been linked with increased risk of hyperlipidaemia and hyperglycaemia. In a cohort of 5672 outpatients with HIV-1 seen at nine US HIV clinics between January, 1993, and January, 2002, the frequency of myocardial infarctions increased after the introduction of protease inhibitors in 1996 (test for trend, p=0.0125). We noted that 19 of 3247 patients taking, but only two of 2425 who did not take, protease inhibitors had a myocardial infarction (odds ratio 7.1, 95% CI 1.6-44.3; Cox proportional hazards model-adjusted for smoking, sex, age, diabetes, hyperlipidaemia, and hypertension-hazard ratio 6.5, 0.9-47.8). Our findings suggest that, although infrequent, use of protease inhibitors is associated with increased risk of myocardial infarction in patients with HIV-1.     

Effect of carboxylesterase 1 c.428G?>?A single nucleotide variation on the pharmacokinetics of quinapril and enalapril

Aim

The aim of the present study was to investigate the effects of the carboxylesterase 1 (CES1) c.428G > A (p.G143E, rs71647871) single nucleotide variation (SNV) on the pharmacokinetics of quinapril and enalapril in a prospective genotype panel study in healthy volunteers.

Methods

In a fixed-order crossover study, 10 healthy volunteers with the CES1 c.428G/A genotype and 12 with the c.428G/G genotype ingested a single 10 mg dose of quinapril and enalapril with a washout period of at least 1 week. Plasma concentrations of quinapril and quinaprilat were measured for up to 24 h and those of enalapril and enalaprilat for up to 48 h. Their excretion into the urine was measured from 0 h to 12 h.

Results

The area under the plasma concentration–time curve from 0 h to infinity (AUC_0–∞) of active enalaprilat was 20% lower in subjects with the CES1 c.428G/A genotype than in those with the c.428G/G genotype (95% confidence interval of geometric mean ratio 0.64, 1.00; P = 0.049). The amount of enalaprilat excreted into the urine was 35% smaller in subjects with the CES1 c.428G/A genotype than in those with the c.428G/G genotype (P = 0.044). The CES1 genotype had no significant effect on the enalaprilat to enalapril AUC_0–∞ ratio or on any other pharmacokinetic or pharmacodynamic parameters of enalapril or enalaprilat. The CES1 genotype had no significant effect on the pharmacokinetic or pharmacodynamic parameters of quinapril.

Conclusions

The CES1 c.428G > A SNV decreased enalaprilat concentrations, probably by reducing the hydrolysis of enalapril, but had no observable effect on the pharmacokinetics of quinapril.     

G?teborg Metoprolol Trial: effects on arrhythmias

During the initial hospitalization, ventricular fibrillation (VF) developed in 6 metoprolol-treated patients (0.9%) vs 17 placebo-treated patients (2.4%) after inclusion in the study (p = 0.035). There were 6 episodes of VF in the metoprolol group compared with 41 episodes in the placebo group (p less than 0.001). During the same period, 14 metoprolol-treated patients had treated ventricular tachycardia vs 26 placebo-treated patients (p = 0.076). Similar favorable results were found when the incidence of severe ventricular arrhythmias during the first rehospitalization within the 3-month double-blind treatment period was analyzed.     

Hepatitis B virus DNA in patients with HBsAg in south western Nigeria

There are about 400 million people with chronic hepatitis B virus (HBV) infection worldwide with a potential of adverse sequelae including hepatocellular carcinoma. Recent data have shown that the level of HBV DNA in serum or plasma of an infected person probably reflects more accurately the replicative activity of the virus and therefore may serve as a better maker for management of the infection. This study was designed to determine the rate of detection of HBV DNA in blood samples of patients with HBsAg positive in Nigeria in comparison with the HBe and anti‐HBe used widely as serological markers of infectivity. Plasma samples from 105 patients with HBsAg positive were tested for the presence of HBeAg and anti‐HBe using a commercial enzyme‐linked immunosorbent assay while plasma HBV DNA was quantified using the COBAS Amplicor HBV Monitor assay. Of the 105 HBsAg samples, 17 (16.2%) and 85 (81%) were positive for HBeAg and anti‐HBe, respectively, while 8 (7.6%) were negative for both HBeAg and anti‐HBe. HBV DNA was detected in 86 (81.9%) of the samples, out of which 15 (18.1%) and 67 (80.7%) were positive for HBeAg and anti‐HBe, respectively. HBV DNA was detected in 78.4% of the HBeAg negative samples and in all the eight samples that were negative for both HBeAg and anti‐HBe. The implication of these findings in the management of patients with HBV infection is compelling. J. Med. Virol. 85:214–218, 2013. © 2012 Wiley Periodicals, Inc.