Codeine and breastfeeding: cases and STIS position

Codeine is commonly used in North America in the postpartum period for pain associated with episotomyand caesarean section. Analgesic properties of codeine are mainly due to its metabolisation intomorphine (5-10%) via CYP2D6. This enzyme is subject to genetic variability, which can alter theamount of active narcotic excreted into breastmilk. A recent case report highlighted this issue, reportingfatal consequences in a newborn whose mother was taking codeine for episiotomy-related pain (1-2). New-born's blood (post-mortem) and mother's milk showed high morphine concentrations. Genotypeanalysis classified the mother as a CYP2D6 ultrarapid metabolizer, a genotype associated withenhanced formation of morphine from codeine. The authors concluded "clinical and laboratory picturewas consistent with opioid toxicity leading to neonatal death". Subsequent comments expressed reasonnabledoubts on this conclusion, though (3-4). Since, anxiety increased about the safety of codeineduring breastfeeding and genetic screening was proposed as a prevention strategy.STIS position:? Codeine with paracetamol is not a usual pain prescription in the postpartum period in Switzerland.This markedly reduces codeine use during lactation in our country, and may partly explain why webarely collected 3 codeine exposures through breastmilk in 15 years at the STIS (all reported afterabove case's publication and without side effects).? Other centrally acting analgesics are not considered safer (5) than codeine during lactation andrequire close observation for somnolence in both the mother and the infant in case of repeated maternaldosage. A lack of monitoring was salient in the case reported above (1).? If the incidence of CYP2D6 polymorphism (1-10% of individuals in Western Europe) (6) can beconsidered of clinical significance, it is not the exclusive predisposing factor to toxic effects. Healthynewborns can be particularly sensitive to even usual doses of narcotic analgesics because of immaturedrug disposition (7). Conditions leading to impaired clearance or increased susceptibility inthe infant (e.g. preterm birth, metabolic diseases) represent further risk factors for opioid toxicity,regardless of the molecule.In conclusion, when prescribed on a large scale, codein can be rarely associated with adverse drugreactions in breastfed infants (8-9). However, other central acting analgesics cannot be considered asinvariably safer. Therefore, paracetamol and well documented NSAID should be used in 1st choiceduring lactation. In case of severe pain, codeine (with paracetamol) remains an acceptable choice butrequires close monitoring, and breastfeeding mothers should be educated regarding risks related toaccumulation in the newborn. Finally, it is doubtful whether CYP2D6 genetic screening would preventall toxic effects, as other risk factors exist for opioids toxicity

Laser-ultraviolet-A induced ultra weak photon emission in human skin cells: A biophotonic comparison between keratinocytes and fibroblasts.

Photons participate in many atomic and molecular interactions and processes. Recent biophysical research has discovered an ultraweak radiation in biological tissues. It is now recognized that plants, animal and human cells emit this very weak biophotonic emission which can be readily measured with a sensitive photomultiplier system. UVA laser induced biophotonic emission of cultured cells was used in this report with the intention to detect biophysical changes between young and adult fibroblasts as well as between fibroblasts and keratinocytes. With suspension densities ranging from 1-8 x 106 cells/ml, it was evident that an increase of the UVA-laser-light induced photon emission intensity could be observed in young as well as adult fibroblastic cells. By the use of this method to determine ultraweak light emission, photons in cell suspensions in low volumes (100 microl) could be detected, in contrast to previous procedures using quantities up to 10 ml. Moreover, the analysis has been further refined by turning off the photomultiplier system electronically during irradiation leading to the first measurements of induced light emission in the cells after less than 10 micros instead of more than 100 milliseconds. These significant changes lead to an improvement factor up to 106 in comparison to classical detection procedures. In addition, different skin cells as fibroblasts and keratinocytes stemming from the same donor were measured using this new highly sensitive method in order to find new biophysical insight of light pathways. This is important in view to develop new strategies in biophotonics especially for use in alternative therapies.

Measurement with an automated oscillometric wrist device with position sensor leads to lower values than measurements obtained with an automated oscillometric arm device from the same manufacturer in elderly persons

Introduction : Le monitoring de la tension artérielle à domicile est recommandé par plusieurs guidelines et a été montré être faisable chez la personne âgée. Les manomètres au poignet ont récemment été proposés pour la mesure de la tension artérielle à domicile, mais leur précision n'a pas été au préalable évaluée chez les patients âgés. Méthode : Quarante-huit participants (33 femmes et 15 hommes, moyenne d'âge 81.3±8.0 ans) ont leur tension artérielle mesurée avec un appareil au poignet avec capteur de position et un appareil au bras dans un ordre aléatoire et dans une position assise. Résultats : Les moyennes de mesures de tension artérielle étaient systématiquement plus basses avec l'appareil au poignet par rapport à celui du bras pour la pression systolique (120.1±2.2 vs. 130.5±2.2 mmHg, P < 0.001, moyenneidéviation standard) et pour la pression diastolique (66.011.3 vs. 69.7±1.3 mmHg, P < 0.001). De plus, une différence de lOmmHg ou plus grande entre l'appareil au bras et au poignet était observée dans 54.2 et 18,8% des mesures systoliques et diastoliques respectivement. Conclusion : Comparé à l'appareil au bras, l'appareil au poignet avec capteur de position sous-estimait systématiquement aussi bien la tension artérielle systolique que diastolique. L'ampleur de la différence est cliniquement significative et met en doute l'utilisation de l'appareil au poignet pour monitorer la tension artérielle chez la personne âgée. Cette étude indique le besoin de valider les appareils de mesures de la tension artérielle dans tous les groupes d'âge, y compris les personnes âgées.

Submicrometer tomography of cells by multiple-wavelength digital holographic microscopy in reflection

We present first results on a method enabling mechanical scanning-free tomography with submicrometer axial resolution by multiple-wavelength digital holographic microscopy. By sequentially acquiring reflection holograms and summing 20 wavefronts equally spaced in spatial frequency in the 485-670 nm range, we are able to achieve a slice-by-slice tomographic reconstruction with a 0.6-1 mum axial resolution in a biological medium. The method is applied to erythrocytes investigation to retrieve the cellular membrane profile in three dimensions.

Variability of ascending aorta diameter measurements as assessed with electrocardiography-gated multidetector computerized tomography and computer assisted diagnosis software.

Recently, morphometric measurements of the ascending aorta have been done with ECG-gated multidector computerized tomography (MDCT) to help the development of future novel transcatheter therapies (TCT); nevertheless, the variability of such measurements remains unknown. Thirty patients referred for ECG-gated CT thoracic angiography were evaluated. Continuous reformations of the ascending aorta, perpendicular to the centerline, were obtained automatically with a commercially available computer aided diagnosis (CAD). Then measurements of the maximal diameter were done with the CAD and manually by two observers (separately). Measurements were repeated one month later. The Bland-Altman method, Spearman coefficients, and a Wilcoxon signed-rank test were used to evaluate the variability, the correlation, and the differences between observers. The interobserver variability for maximal diameter between the two observers was up to 1.2 mm with limits of agreement [-1.5, +0.9] mm; whereas the intraobserver limits were [-1.2, +1.0] mm for the first observer and [-0.8, +0.8] mm for the second observer. The intraobserver CAD variability was 0.8 mm. The correlation was good between observers and the CAD (0.980-0.986); however, significant differences do exist (P<0.001). The maximum variability observed was 1.2 mm and should be considered in reports of measurements of the ascending aorta. The CAD is as reproducible as an experienced reader.

Perfusion computed tomography-guided subacute endovascular reperfusion in a patient with carotid occlusion.

Most patients with symptomatic internal carotid artery occlusion have a single minor or major hemispheric stroke. A minority of patients have ipsilateral retinal ischemia, recurrent strokes, or transient ischemic attacks. Whereas spontaneous carotid recanalization is rare, acute surgical recanalization has been attempted, with mixed results. Recently, acute endovascular recanalization has been performed and described as feasible and relatively safe. We describe a patient with symptom recurrence related to hemodynamic factors after occlusion of the carotid artery who was successfully treated 14 days after symptom onset.

Assessment of coronary stenosis, plaque burden and remodeling by multidetector computed tomography in patients referred for suspected coronary artery disease.

Aims To compare multidetector computed tomography (MDCT) with intravascular ultrasound (IVUS) and invasive quantitative coronary angiography (QCA) for assessment of coronary lesions in patients referred for suspected coronary artery disease (CAD). Methods and results We studied 57 patients (48 men; mean age: 63 +/- 10 years) who underwent 64-slice MDCT because of atypical chest pain, stable angina, or ECG abnormalities and were diagnosed with CAD. All patients subsequently underwent QCA and IVUS. We analyzed 102 coronary lesions using the three techniques. Measurements of luminal area stenosis and cross-sectional area by MDCT (72.9 +/- 7.0% and 4.5 +/- 1.8 mm(2), respectively) were in good agreement with those by IVUS [72.7 +/- 6.7% and 4.5 +/- 1.6 mm(2), respectively; Lin's concordance correlation coefficient r = 0.847; 95% confidence interval (CI) = 0.792-0.902 and r = 0.931; 95% CI = 0.906-0.956, respectively] but not QCA (r = 0.115; 95% CI = 0.040-0.189 and r = 0.433; 95% CI = 0.291-0.576, respectively). Plaque cross-sectional area and plaque volume measured by MDCT (12.4 +/- 3.8 mm(2) and 104.7 +/- 52.8 mu l, respectively) were in good agreement with those by IVUS (12.2 +/- 3.7 mm(2) and 102.8 +/- 54.1 mu l; r = 0.913; 95% CI = 0.880-0.945 and r = 0.979; 95% CI = 0.969-0.990, respectively). Remodeling index measurements by MDCT (1.22 +/- 0.22) were in good agreement with those by IVUS (r = 0.876; 95% CI = 0.831-0.922). Positive remodeling occurred in 63% of stenoses. Conclusion MDCT allows accurate noninvasive assessment of coronary stenosis, plaque burden and remodeling in patients referred for suspected CAD. Positive remodeling is a frequent finding in stable lesions. J Cardiovasc Med 12:122-130 (C) 2011 Italian Federation of Cardiology.

Low-dose multidetector computed tomography of the cervical spine: optimization of iterative reconstruction strength levels.

BACKGROUND: Iterative reconstruction (IR) techniques reduce image noise in multidetector computed tomography (MDCT) imaging. They can therefore be used to reduce radiation dose while maintaining diagnostic image quality nearly constant. However, CT manufacturers offer several strength levels of IR to choose from. PURPOSE: To determine the optimal strength level of IR in low-dose MDCT of the cervical spine. MATERIAL AND METHODS: Thirty consecutive patients investigated by low-dose cervical spine MDCT were prospectively studied. Raw data were reconstructed using filtered back-projection and sinogram-affirmed IR (SAFIRE, strength levels 1 to 5) techniques. Image noise, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) were measured at C3-C4 and C6-C7 levels. Two radiologists independently and blindly evaluated various anatomical structures (both dense and soft tissues) using a 4-point scale. They also rated the overall diagnostic image quality using a 10-point scale. RESULTS: As IR strength levels increased, image noise decreased linearly, while SNR and CNR both increased linearly at C3-C4 and C6-C7 levels (P < 0.001). For the intervertebral discs, the content of neural foramina and dural sac, and for the ligaments, subjective image quality scores increased linearly with increasing IR strength level (P ≤ 0.03). Conversely, for the soft tissues and trabecular bone, the scores decreased linearly with increasing IR strength level (P < 0.001). Finally, the overall diagnostic image quality scores increased linearly with increasing IR strength level (P < 0.001). CONCLUSION: The optimal strength level of IR in low-dose cervical spine MDCT depends on the anatomical structure to be analyzed. For the intervertebral discs and the content of neural foramina, high strength levels of IR are recommended.

Position of fixed-dose combinations containing an AT(1)-receptor blocker and a thiazide diuretic.

Treatment of hypertension remains a difficult task despite the availability of different types of medications lowering blood pressure by different mechanisms. In order to reach the target blood pressures recommended today combination therapy is required in most patients. The co-administration of two drugs with different impacts on the cardiovascular system markedly increases the antihypertensive effectiveness without altering adversely tolerability. Fixed low-dose combinations are becoming a valuable option not only as second-line, but also as first-line therapy. In this respect the co-administration of thiazide diuretic with an AT(1)-receptor blocker is particularly appealing. The diuretic-induced decrease in total body sodium activates the renin-angiotensin system, thus rendering blood pressure maintenance angiotensin II-dependent. During blockade of the renin-angiotensin system low doses of thiazides generally suffice, allowing the prevention of undesirable metabolic effects. Also, blockade of the AT(1)-receptor, particularly when angiotensin II production is enhanced in response to diuretic therapy, is expected to be beneficial, since angiotensin II seems to contribute importantly to the pathogenesis of cardiovascular and renal complications of hypertension.

Measurement with an automated oscillometric wrist device with position sensor leads to lower values than measurements obtained with an automated oscillometric arm device from the same manufacturer in elderly persons.

OBJECTIVE: Home blood pressure (BP) monitoring is recommended by several clinical guidelines and has been shown to be feasible in elderly persons. Wrist manometers have recently been proposed for such home BP measurement, but their accuracy has not been previously assessed in elderly patients. METHODS: Forty-eight participants (33 women and 15 men, mean age 81.3±8.0 years) had their BP measured with a wrist device with position sensor and an arm device in random order in a sitting position. RESULTS: Average BP measurements were consistently lower with the wrist than arm device for systolic BP (120.1±2.2 vs. 130.5±2.2 mmHg, P<0.001, means±SD) and diastolic BP (66.0±1.3 vs. 69.7±1.3 mmHg, P<0.001). Moreover, a 10 mmHg or greater difference between the arm and wrist device was observed in 54.2 and 18.8% of systolic and diastolic measures, respectively. CONCLUSION: Compared with the arm device, the wrist device with position sensor systematically underestimated systolic as well as diastolic BP. The magnitude of the difference is clinically significant and questions the use of the wrist device to monitor BP in elderly persons. This study points to the need to validate BP measuring devices in all age groups, including in elderly persons.

Distribution of artifactual gas on post-mortem multidetector computed tomography (MDCT).

PURPOSE: We investigated the incidence and distribution of post-mortem gas detected with multidetector computed tomography (MDCT) to identify factors that could distinguish artifactual gas from cardiac air embolism. MATERIAL AND METHODS: MDCT data of 119 cadavers were retrospectively examined. Gas was semiquantitatively assessed in selected blood vessels, organs, and body spaces (82 total sites). RESULTS: Seventy-four of the 119 cadavers displayed gas (62.2%; CI 95% 52.8-70.9), and 56 (75.7%) displayed gas in the heart. Most gas was detected in the hepatic parenchyma (40%), right heart (38% ventricle, 35% atrium), inferior vena cava (30% infrarenally, 26% suprarenally), hepatic veins (26% left, 29% middle, 22% right), and portal spaces (29%). Male cadavers displayed gas more frequently than female cadavers. Gas was detected 5-84 hours after death; therefore, the post-mortem interval could not reliably predict gas distribution (rho = 0.719, p < 0.0001). We found that a large amount of putrefaction-generated gas in the right heart was associated with aggregated gas bubbles in the hepatic parenchyma (sensitivity = 100%, specificity = 89.7%). In contrast, gas in the left heart (sensitivity = 41.7%, specificity = 100%) or in periumbilical subcutaneous tissues (sensitivity = 50%, specificity = 96.3%) could not predict gas due to putrefaction. CONCLUSION: This study is the first to show that the appearance of post-mortem gas follows a specific distribution pattern. An association between intracardiac gas and hepatic parenchymal gas could distinguish between post-mortem-generated gas and vital air embolism. We propose that this finding provides a key for diagnosing death due to cardiac air embolism.

Dépistage du cancer pulmonaire par scanner thoracique [Computed tomography screening for lung cancer].

Lung cancer screening has been the focus of intense interest since the publication in 2011 of the NLST trial (National Lung Screening Trial) showing a mortality reduction in smokers undergoing 3-year screening by chest computed tomography. Although these data appear promising, many issues remain to be resolved, such as high rate of false positive cases, risk of overdiagnosis, optimal intervals between screens, duration of the screening process, feasibility, and cost. Structured screening programs appear crucial to guarantee patient information, technical quality, and multidisciplinary management. Despite these uncertainties, several guidelines already state that screening should be performed in patients at risk, whereas investigators stress that more data are needed. How should the primary care physician deal with individual patients requests? This review provides some clues on this complex issue.