Association of a functional polymorphism in the CYP4A11 gene with systolic blood pressure in survivors of myocardial infarction

OBJECTIVE: Survivors of myocardial infarction (MI) are known to have a high prevalence of arterial hypertension which, at the same time, imposes a major risk to such patients. Genetic variants of the arachidonic acid monooxygenase CYP4A11 may result in decreased synthesis of 20-hydroxyeicostatetraenoic acid (20-HETE), experimental hypertension and elevated blood pressure levels in humans. The present study aimed to investigate the impact of the functionally relevant T8590C polymorphism of this gene on blood pressure and the prevalence of hypertension in MI patients. METHODS: Survivors of MI from the MONICA Augsburg MI registry (n = 560) were studied after a mean of 5.6 years after the acute event. Participants were examined by standardized anthropometric and echocardiographic measurements, as well as genotyping for CYP4A11 T8590C allele status. RESULTS: Genotype frequencies in MI patients (TT = 71.8%, CT = 26.2%, CC = 2.0%) did not differ from those in population-based controls (n = 1363; TT = 75.4%, CT = 22.5% and CC = 2.1%, P = 0.22). MI survivors with the CC genotype displayed higher systolic blood pressure levels (CC: 143.4 +/- 4.9 mmHg versus CT: 134.5 +/- 1.3 mmHg and TT: 131.1 +/- 0.8 mmHg; P = 0.02) and a non-significant trend towards higher diastolic blood pressure levels (CC: 88.4 +/- 3.0 mmHg versus CT: 84.9 +/- 0.8 mmHg and TT: 83.9 +/- 0.5 mmHg; P = 0.17) in multivariate models. Accordingly, the C allele was related to elevated odds ratios for hypertension in a recessive [4.14; 95% confidence interval (CI) = 1.07-15.96, P = 0.04] and in a dominant model (1.50; 95% CI = 1.03-2.20, P = 0.04), respectively. No blood pressure-independent association of the T8590C polymorphism with echocardiographic parameters of left ventricular function and/or geometry was found. CONCLUSION: The data obtained in the present study strengthen the evidence of an association of the CYP4A11 T8590C polymorphism with blood pressure levels and hypertension prevalence. Particularly, the risk of arterial hypertension is substantially higher in MI patients homozygous for the CC allele. By contrast, no evidence was obtained for an association between this genotype and MI.     

Transforming the surgical "time-out" into a comprehensive "preparatory pause"

We propose expansion of the standard "time-out" into a comprehensive "preparatory pause" encompassing five well-documented perioperative risk avoidance strategies: beta-adrenergic blockade, DVT prophylaxis, preoperative antibiotics, normothermia, and euglycemia. Although all members of the surgical team acknowledge the clear benefit of these five prophylactic strategies, published national compliance even in the target patient population is a disappointingly consistent 50%. We have developed and field-tested a "preparatory pause" form that we appended to our "surgical time-out." By politely challenging our surgical team as to the inclusion of these five risk avoidance strategies in 167 consecutive patients, we increased our compliance to more than 90% for each preventive measure. We have not attempted to quantify the physical and psychological benefit of complication avoidance due to the enhanced activation of these five prophylactic strategies. Using published surgical complication prevalence data, with and without these accepted risk avoidance measures, we estimate the number of complications per 100 patients avoided. Utilizing the Medicare payment schedule for each complication, we approximate the purely financial benefit of the "preparatory pause" to be $88,640 per 100 patients, or almost $900 per patient. The now standard surgical "time-out" is designed to avoid the gratifyingly uncommon problem of "wrong patient,"wrong procedure," and "wrong site." Many surgeons negotiate an entire career without stumbling over these disastrous problems. We propose expansion of the "time-out" to include five well-documented perioperative risk avoidance strategies that many of us overlook all too often.     

Running in pregnancy transiently increases postnatal hippocampal neurogenesis in the offspring

Voluntary wheel running of mice in pregnancy and lactation led to a twofold increase in hippocampal precursor-cell proliferation and in the number of Prox1-expressing lineage-determined cells at postnatal day 8 (P8). At P36, the number of newly generated granule cells approximately doubled, resulting in a 40% higher total number of granule cells in pups from running dams as compared with controls. Cell proliferation at embryonic day 15 (E15), in contrast, was decreased in the progeny of exercising mice, and the birth weight was reduced. At P49, body weight had normalized, and hippocampal neurogenesis was not different between the two groups. mRNA for FGF2 was expressed at higher levels at E15 and P8 in runner pups, whereas VEGF was increased only at E15. Insulin-like growth factor did not show differences at any time point. At P36, no differences for any of the factors were found. Our data indicate that maternal behavior and physical activity affects infantile growth-factor expression and can transiently stimulate postnatal hippocampal development in the offspring.     

Impact of the operator's experience on value of high-resolution transabdominal ultrasound in the diagnosis of choledocholithiasis: a prospective comparison using endoscopic retrograde cholangiography as the gold standard

OBJECTIVE: Transabdominal ultrasound (US) is the most frequently used imaging method for the diagnosis of choledocholithiasis. The aim of this prospective study was to evaluate the diagnostic accuracy of high-resolution US in the diagnosis of common bile duct stones depending on the operator's experience and in comparison with endoscopic retrograde cholangiography (ERC) as the gold standard. MATERIAL AND METHODS: From April 2003 through November 2004, 126 patients referred because of clinically and biochemically suspected common bile duct stones were included in the study. Two patients were excluded because they refused to undergo ERC. Consequently, the study comprised 124 patients (86 F, 38 M, mean age 63.2 years, range 21-91 years). High-resolution US was performed (2-5 MHz sector scanner; Siemens Elegra, Erlangen, Germany) by operators who were unaware of the results of other imaging procedures. The definitive diagnosis was established by means of ERC. RESULTS: Thirty-five out of 124 patients were investigated by experienced examiners. Twenty-seven of 35 patients (77%) were found to have stones at ERC. Bile duct stones were correctly found by US in 22 out of 27 patients (sensitivity 82%, 95% CI: 63-92). Of the 8 patients without stones at ERC, one false-positive diagnosis was made with US (specificity 88%, 95% CI: 53-98). Correct diagnoses were made in 29 out of 35 (accuracy 83%, 95% CI: 67-92) patients investigated by experienced examiners. Eighty-nine out of 124 patients were investigated by less-experienced examiners. Fifty-four of 89 patients (61%) were found to have stones at ERC. Choledocholithiasis was found correctly in only 25 out of 54 patients (sensitivity 46%, 95% CI: 34-59). Of the 35 patients without stones at ERC, three false-positive diagnoses were made with US (specificity 91%, 95% CI: 78-97). In conclusion, correct diagnoses were observed in 57 of 89 patients (accuracy 64%, 95% CI: 54-73) investigated by less-experienced examiners (p<0.05 in comparison with the results of experienced examiners). CONCLUSIONS: High-resolution US carried out by experienced examiners has a high diagnostic accuracy in the diagnosis of choledocholithiasis. Therefore, good training and continued experience are prerequisites for successful sonographic detection of bile duct stones using US. Under these conditions, further expensive and invasive methods such as ERC, magnetic resonance cholangiopancreatography and endoscopic ultrasonography may not be necessary in cases with a clear sonographic diagnosis.     

Positive effects of growth at suboptimal temperature and high salt concentration on long-term survival of Lactobacillus sakei

Lactobacillus sakei is a lactic acid bacterium commonly found on fresh meat and represents the predominant flora of vacuum-packed meat. In the present article, we studied the behavior of L. sakei in a chemically defined medium under various growth conditions relative to temperature or NaCl concentration. Growth occurred at each temperature, but growth rate and final cell density decreased at low temperature and survival was enhanced. In the presence of NaCl, we also observed a longer doubling time and a lower final cell density together with an enhanced long-term survival. When both conditions were combined, the long-term survival was greatly increased to about 28 weeks. Differences in cell morphology were observed under electron microscopy when cells were grown at low temperature in the presence of salt. We speculate that these are due to modifications in membrane structure. These results show that L. sakei is able to adapt to these environmental conditions and that slow growth is clearly associated with enhanced long-term survival.     

Childhood abuse and neglect and transitions in stages of alcohol involvement among women: A latent transition analysis approach

Background

Childhood abuse and neglect have been linked with alcohol disorders in adulthood yet less is known about the potential of early trauma to influence transitions in stages of alcohol involvement among women. Study aims were to (1) identify stages of women's alcohol involvement, (2) examine the probability of transitions between stages, and (3) investigate the influence of four domains of childhood abuse and neglect (sexual abuse, physical abuse, neglect, and witness to domestic violence), assessed individually and as poly-victimization, on transitions.

Methods

The sample consisted of 11,750 adult female current drinkers identified in Wave 1 (2001–2002) and re-interviewed in Wave 2 (2004–2005) of the National Epidemiological Survey on Alcohol and Related Conditions.

Results

Three stages of alcohol involvement emerged from latent class analysis of 11 DSM-IV abuse/dependence criteria: severe (1.5% at Wave 1, 1.9% at Wave 2), hazardous (13.6% at Wave 1, 16.0% at Wave 2), and non-problem drinking (82.1% at Wave 1, 84.5% at Wave 2). Adjusted latent transition analyses determined transition probabilities between stages across waves. Women reporting any childhood abuse and neglect were more likely to advance from the non-problem drinking class at Wave 1 to severe (AOR = 3.90, 95% CI = 1.78–8.53) and hazardous (AOR = 1.56, 95% CI = 1.22–2.01) drinking classes at Wave 2 relative to women without this history. Associations were also observed between individual domains and transition from no problems to severe alcohol stage.

Conclusions

Results suggest a long-term impact of childhood abuse and neglect as drivers of progression in women's alcohol involvement.