Genetic Variation in Sex Hormone Genes Influences Heel Ultrasound Parameters in Middle‐Aged and Elderly Men: Results From the European Male Aging Study (EMAS)

Genes involved in sex hormone pathways are candidates for influencing bone strength. Polymorphisms in these genes were tested for association with heel quantitative ultrasound (QUS) parameters in middle‐aged and elderly European men. Men 40–79 yr of age were recruited from population registers in eight European centers for the European Male Aging Study (EMAS). Polymorphisms were genotyped in AR, ESR1, ESR2, CYP19A1, CYP17A1, SHBG, SRD5A2, LHB, and LHCGR. QUS parameters broadband ultrasound attenuation (BUA) and speed of sound (SOS) were measured in the heel and used to derive BMD. The relationships between QUS parameters and polymorphisms were assessed using linear regression adjusting for age and center. A total of 2693 men, with a mean age of 60.1 ± 11.1 (SD) yr were included in the analysis. Their mean BUA was 80.0 ± 18.9 dB/Mhz, SOS was 1550.2 ± 34.1 m/s, and BMD was 0.542 ± 0.141 g/cm². Significant associations were observed between multiple SNPs in a linkage disequilibrium (LD) block within CYP19A1, peaking at the TCT indel with the deletion allele associating with reduced ultrasound BMD in heterozygotes (β =?0.016, p = ?0.005) and homozygotes (β = ?0.029, p = 0.001). The results for BUA and SOS were similar. Significant associations with QUS parameters were also observed for the CAG repeat in AR and SNPs in CYP17A1, LHCGR, and ESR1. Our data confirm evidence of association between bone QUS parameters and polymorphisms in CYP19A1, as well as modest associations with polymorphisms in CYP17A1, ESR1, LHCGR, and AR in a population sample of European men; this supports a role for genetically determined sex hormone actions in influencing male bone health.     

Development and daily use of an electronic oncological patient record for the total management of cancer patients: 7 years' experience

Background: We describe our experience with an electronic oncologicalpatient record (EOPR) for the total management of cancer patients. Methods: The web-based EOPR was developed on the basis of auser-centred design including user education and training, followedby continuous assistance; user acceptance was monitored by meansof three questionnaires administered after 2 weeks, 6 monthsand 6 years. Results: The EOPR has been used daily for all in-ward, day hospitaland ambulatory clinical activities since July 2000. The mostwidely appreciated functions are its rapid multipoint access,the self-updated summary of the patients’ clinical course,the management of the entire therapeutic programme synchronisedwith working agendas and oncological teleconsultation. Securityand privacy are assured by means of the separate storage ofclinical and demographic data, with access protected by loginand a password. The questionnaires highlighted appreciationof rapid data retrieval and exchange and the perception of improvedquality of care, but also revealed a sense of additional workand a negative impact on doctor–patient relationships. Conclusions: Our EOPR has proved to be effective in the totalmanagement of cancer patients. Its user-centred design and flexibleweb technology have been key factors in its successful implementationand daily use. Key words: cancer patient management, digital record, electronic patient record Received for publication February 18, 2008. Revision received July 18, 2008. Accepted for publication July 21, 2008.     

Lamivudine treatment for acute hepatitis B after liver transplantation

Background/Aims: Acute hepatitis caused by recurrent or de novo hepatitis B virus (HBV) infection after liver transplantation frequently induces aggressive disease leading to liver failure. To aim of this study was to determine the efficacy and safety of lamivudine treatment in post-transplant acute hepatitis B.Method: Twelve patients with acute hepatitis B were started on lamivudine 100 mg po daily within 8 weeks of the appearance of HBsAg. One patient was excluded after 1 month because of hepatocellular carcinoma recurrence. Patients were followed for an average of 68.6 weeks (range 32–108), and were clinically and biochemically evaluated on a monthly basis. They had a histological assessment at baseline, after at least 6 months, and whenever clinically indicated.Results: Basal HBV-DNA ranged between 13 and 1288 pg/ml and serum alanine aminotransferase between 97 and 1036 U/l. HBV-DNA became undetectable within 8 weeks and transaminases normalized within 24 weeks in all cases. At the last visit, eight patients (73%) remained HBV-DNA negative by liquid hybridization and had normal or close to normal alanine aminotransferase. Five patients (45%) were also HBsAg negative and HBV-DNA negative by polymerase chain reaction. HBV-DNA and transaminase breakthrough occurred in three patients (27%). Histology after 6–9 months showed chronic hepatitis in seven patients. Lamivudine was well tolerated without serious adverse reactions.Conclusions: These results indicate that lamivudine treatment induces sustained inhibition of viral replication and normalization of transaminases in the majority of post-transplant patients with acute hepatitis B. HBsAg loss may be achieved in a considerable number of cases. Although viral resistance is relatively frequent, early initiation of lamivudine appears to be effective and safe.     

Physical activity reduces the risk for hospitalizations in patients with type 2 diabetes

The purpose of this study is to examine factors and variables associated with hospitalizations in type 2 diabetes mellitus (T2DM). This is a 2-year follow-up study of 145 patients (87 women/58 men), mean age 55.0 ± 3.3 (40 to 60). At baseline, comorbidity severity was evaluated by the Charlson Comorbidity Index (CCI), depressive symptoms by the Beck Depression Inventory (BDI II), sleep quality by the Pittsburgh Sleep Quality Index, daytime sleepiness by the Epworth Sleepiness Scale, and levels of physical activity by the International Physical Activity Questionnaire (IPAQ). Arterial hypertension (74 %), cardiovascular pathology (30 %), and stroke (10 %) were found at baseline. After 2 years, eight cases (6 %) developed a new stroke. At baseline, 70 % (N = 102) of patients had a sedentary life, and 30 % (N = 43) were irregularly active. Two years later, the number of patients with a sedentary life decreased to 52 % (N = 76), and an increase of irregularly active (35 %, N = 51) and active patients (13 %, N = 18; p < 0.005) was observed. Twenty-four individuals (16 %) reported at least one hospitalization. Logistic regression analysis showed that the presence of hypertension and lower physical activity status (IPAQ levels) were predictors of hospitalizations (OR = 0.34, CI 0.14–0.85, p = 0.02); lower physical activity status remained significant in the presence of hypertension (OR = 0.33, CI 0.13–0.84, p = 0.02). In conclusion, higher physical activity status is an independent predictor of lower hospitalizations in T2DM proving that exercising is an important strategy not only to reduce health care costs but also to improve the human burden of hospitalizations for the patients.

     

Prevalence of metabolic syndrome in long-term survivors of hematopoietic stem cell transplantation

Our purpose was to determine the prevalence and features of metabolic syndrome (MS) in a series of long-term hematopoietic stem cell transplantation (HSCT) survivors. We assessed the clinical, metabolic and endocrinological data, and plasma TNF, leptin, resistin and adiponectin levels relating to 85 HSCT recipients. MS was diagnosed on the basis of the National Cholesterol Education Program-Adult Treatment Panel III criteria. Its prevalence was compared with that observed in an Italian population, and its relationship with the clinical and laboratory parameters was assessed univariately and multivariately. Twenty-nine HSCT recipients had MS instead of the 12.8 expected (P<0.0001), with hypertriglyceridemia being the most common feature. Univariate analysis indicated that high insulin and leptin levels, low-adiponectin levels and hypogonadism were significantly related to a diagnosis of MS; multivariate analysis indicated plasma leptin, insulin resistance, age and hypogonadism. We conclude that HSCT recipients are at increased risk of a form of MS that has particular clinical features. Plasma leptin levels are independently related to MS, thus suggesting that leptin resistance may play a role as a pathogenetic clue, as in other conditions in which MS occurs as a secondary phenomenon. MS deserves consideration as a life-threatening complication in patients who are probably cured of their underlying disease.     

The use of phosphodiesterase 5 inhibitors with concomitant medications

The phosphodiesterase-5 inhibitors (PDE5i) sildenafil, vardenafil, and tadalafil are considered first-line therapy for the treatment of patients with erectile dysfunction (ED). In addition to the classical pro-erectile-effect, clinical findings have suggested that they can also influence vascular tone in pulmonary, coronary and other vascular tissues, as well as improving symptoms associated with benign prostatic hyperplasia. Therefore, considering the hypothetical widespread application of PDE5i, the potential for drug-drug interactions emerges as a relevant factor in determining the safety profile of PDE5i. Review of relevant literature was conducted using data sources from MEDLINE (1998, to June 2007). The use of nitrates remains the only contraindication for all 3 PDE5i. Vardenafil is also not recommended in patients taking type 1A (such as quinidine, or procainamide) or type 3 antiarrhythmics (such as sotalol, or amiodarone) while no other major limitations have been reported for tadalafil and sildenafil. In contrast to previously reported labeling, recent studies have suggested only a precaution, but not contraindication with the concomitant use of alpha-blockers agents. In addition, precaution is also suggested in the presence of potent CYP3A inhibitors, such as azole antifungals, antiretroviral protease inhibitors, or macrolid antibiotics. This is because sildenafil, vardenafil, and tadalafil are metabolized mainly via the CYP3A4 pathway. On the other hand, statins and testosterone seem to have synergic effects with PDE5i on sexual activity.     

Water quality criteria assessment for chlorinated benzenes using the quantitative structure activity relation approach and porphyrogenic endpoint in rats

Sub‐chronic toxicity data on rats for various chlorobenzenes have been utilized to show a high correlation between log dose porphyria and log P, the log of the octanol:water partition coefficient. Various predictive equations were calculated as a function of log P (log P)² log P + (log P)² log 1/S_W and (log 1/S_w)². All have good correlations except for the case of (log 1/S_w)². The calculated log criterion values obtained from predicted dose for porphyria in rats were regressed against log P and the log of the bioconcentration factor (log B) and various single and multi‐parameter regression equations were found. Criteria predicted from log P values and sub‐chronic toxicity data tended to be between 10–100 times larger than criteria calculated by other means (chronic toxicity, carcinogenicity or organoleptic). This quantitative structure activity relation approach has the advantage of providing criteria for all congeners in a series, whether or not they have been tested for carcinogenicity.