Single-dose and steady-state pharmacokinetics of diltiazem administered in two different tablet formulations.

Single-dose and steady state pharmacokinetics of diltiazem administered in two different oral formulations were assessed with particular reference to rate and extent of absorption. Following single dose administration a significant difference in tmax was observed (2.9 +/- 1.9 and 6.8 +/- 2.6 hr respectively) whereas differences in AUC, t1/2 and Cmax were not significant. The AUC (mean +/- S.D.) values following single dose administration of Cardil and Cardizem were 678.4 +/- 321.5 and 948.6 +/- 580.6 ng.ml-1.hr respectively. The mean and the 95% confidence limits for the observed ratio AUCCardil/AUCCardizem are 0.89 and 0.44-1.34 respectively. At steady-state a significant difference between Cmax/Cmin and tmax was seen Cmax/Cmin being 4.9 and 3.2 respectively and Tmax being 2.7 +/- 2.0 and 6.0 +/- 2.8 hr respectively, whereas Cmax and AUC did not differ significantly. The AUC (mean +/- S.D.) values in steady state of Cardil and Cardizem were 880.1 +/- 399.8 and 1056.8 +/- 509.8 ng.ml-1.hr respectively. The mean and the 95% confidence limits for the observed ratio AUCCardil/AUCCardizem are 0.96 and 0.66-1.26 respectively. Although the observed ratios AUCCardil/AUCCardizem in both the single-dose and the steady-state study do not differ significantly from 1.0, the confidence limits exceed the acceptable values given by Poulsen & Juul (personal communication 1990) (a 20% decrease or increase of the ratio to 0.8 or 1.2).     

Implementation of percutaneous dilation tracheotomy – value of preincisional ultrasonic examination?

BACKGROUND: In this observational study we have evaluated the implementation of percutaneous dilation tracheotomy (PDT), using the forceps dilation technique (Portex) in a multidisciplinary ICU. METHODS: We included a preincisional ultrasonic evaluation of the neck in order to visualise the isthmus glandula thyroidea and major vessels. The observational period comprised one year. PDT was performed in 28 patients. RESULTS: Implementation of PDT was uneventful. Duration of insertion was 10 min (4-40 min). Total time of tracheostomy was 8 days (1-65 days). In nine cases, the proximal end of the isthmus was overlying the space between the 1st and 2nd tracheal ring, which was considered the optimal insertion site. This resulted in seven cases of insertion between the cricoidea and the 1st tracheal ring and in two cases in a more distal insertion. Nineteen tracheotomies were performed in the interstice between the 1st and 2nd tracheal ring. In nine patients, major vessels were overlying the trachea. In none of the patients did this information result in an altered insertion site. Two cases of minor bleeding were observed; both stopped upon compression. In two patients the primary tube size (8.0) was too big and a smaller tube had to be inserted. In one patient the tube was maladapted to the stoma and had to be interchanged with an ordinary tracheostomial tube on the 5th day of tracheostomy. CONCLUSION: Based on the experience gathered in this study and information from the literature, we have abandoned the routine use of ultrasonic examination of the neck prior to PDT. In order to achieve and maintain routine, we suggest that the procedure is performed by a restricted number of doctors.     

Pharmacokinetics of remifentanil and its major metabolite, remifentanil acid, in ICU patients with renal impairment

Background. The pharmacokinetics of remifentanil, an opioidanalgesic metabolized by non-specific esterases, and its principalmetabolite, remifentanil acid (RA), which is excreted via thekidneys, were assessed as part of an open-label safety studyin intensive care unit (ICU) patients with varying degrees ofrenal impairment. Methods. Forty adult ICU patients with normal/mildly impairedrenal function (creatinine clearance [CL_cr] 62.9 (SD) 14.5 mlmin^–1; n=10) or moderate/severe renal impairment (CL_cr14.7 (15.7) ml min^–1; n=30) were included. Remifentanilwas infused for up to 72 h, at a starting rate of 6–9µg kg^–1 h^–1 titrated to achieve a target sedationlevel, with additional propofol (0.5 mg kg^–1 h^–1)if required. Intensive arterial sampling was performed for upto 72 h after infusion. Pharmacokinetic parameters obtainedby simultaneous modelling of remifentanil and RA data were statisticallycompared between the two groups. Results. Remifentanil pharmacokinetics were not significantlyaffected by renal status. RA clearance in the moderate/severegroup was reduced to about 25% that of the normal/mild group(41 (29) vs 176 (49) ml kg^–1 h^–1, P<0.0001).Metabolic ratio, a predictor of the ratio of RA to remifentanilconcentrations at steady state, was approximately eight-foldhigher in the moderate/severe group relative to the normal/mildgroup (116 (110) vs 15 (4), P<0.0001). Maximum RA levelsapproached 700 ng ml^–1 in the moderate/severe group. Conclusions. Although RA accumulates in patients with moderate/severerenal impairment, pharmacokinetic modelling predicts that RAconcentrations during a 9 µg kg^–1 h^–1 remifentanilinfusion for up to 15 days would not exceed those reported inthe present study, for which no associated prolongation of µ-opioideffects was observed. Br J Anaesth 2004; 92: 493–503     

Male reproductive organs are at risk from environmental hazards

Male reproductive disorders that are of interest from an environmental point of view include sexual dysfunction,infertility,cryptorchidism,hypospadias and testicular cancer. Several reports suggest declining sperm counts and increase of these reproductive disorders in some areas during some time periods past 50 years. Except for testicular cancer this evidence is circumstantial and needs cautious interpretation. However,the male germ line is one of the most sensitive tissues to the damaging effects of ionizing radiation,radiant heat and a number of known toxicants. So far occupational hazards are the best documented risk factors for impaired male reproductive function and include physical exposures （radiant heat,ionizing radiation,high frequency electromagnetic radiation）,chemical exposures （some solvents as carbon disulfide and ethylene glycol ethers,some pesticides as dibromochloropropane,ethylendibromide and DDT/DDE,some heavy metals as inorganic lead and mercury） and work processes such as metal welding. Improved working conditions in affluent countries have dramatically decreased known hazardous workplace exposures,but millions of workers in less affluent countries are at risk from reproductive toxicants.New data show that environmental low-level exposure to biopersistent pollutants in the diet may pose a risk to people in all parts of the world. For other toxicants the evidence is only suggestive and further evaluation is needed before conclusions can be drawn. Whether compounds as phthalates,bisphenol A and boron that are present in a large number of industrial and consumer products entails a risk remains to be established. The same applies to psychosocial stressors and use of mobile phones. Finally,there are data indicating a particular vulnerability of the fetal testis to toxicants-for instance maternal tobacco smoking. Time has come where male reproductive toxicity should be addressed form entirely new angles including exposures very early in life.     

Ten years’ experience of free flaps for breast reconstruction in a Danish microsurgical centre: An audit

We have done a total of 292 breast reconstructions using a free flap over a period of 10 years (1994–2003). During the last five years the number of deep inferior epigastric perforator (DIEP) flaps has increased. However, to secure an optimal blood supply we still use a muscle-sparing transverse rectus abdominis musculocutaneous (TRAM) flap sometimes. Our results with the two flaps were identical as far as operating time and length of hospital stay were concerned, but the DIEP flap has less donor site morbidity. Our results are influenced by our selection of patients and our technique but we think that muscle-sparing TRAM flaps may be used as an alternative to DIEP flaps.     

Environmental mercury exposure,semen quality and reproductive hormones in Greenlandic Inuit and European men: a cross-sectional study

Several animal studies indicate that mercury is a male reproductive toxicant, but human studies are few and contradictory. We examined semen characteristics and serum levels of reproductive hormones in relation to environmental exposure to mercury. Blood and semen samples were collected from 529 male partners of pregnant women living in Greenland, Poland and Ukraine between May 2002 and February 2004. The median concentration of the total content of mercury in whole blood was 9.2 ng ml⁻¹ in Greenland (0.2–385.8 ng ml⁻¹), 1.0 ng ml⁻¹ in Poland (0.2–6.4 ng ml⁻¹) and 1.0 ng ml⁻¹ in Ukraine (0.2–4.9 ng ml⁻¹). We found a significantly positive association between the blood levels of mercury and serum concentration of inhibin B in men from Greenland (β=0.074, 95% confidence interval (CI)=0.021 to 0.126) and in an analysis including men from all three regions (β=0.067, 95% CI=0.024 to 0.110). The association may be due to beneficial effects of polyunsaturated fatty acids (PUFAs), which are contained in seafood and fish. No significant association (P>0.05) was found between blood concentrations of mercury and any of the other measured semen characteristics (semen volume, total sperm count, sperm concentration, morphology and motility) and reproductive hormones (free androgen index (FAI), follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone and LH×testosterone) in any region. In conclusion, the findings do not provide evidence that environmental mercury exposure in Greenlandic and European men with median whole blood concentration up to 10 ng ml⁻¹ has adverse effects on biomarkers of male reproductive health.     

Changes in perceived social support and PTSD symptomatology among Danish army military personnel

Purpose

Previous research has identified social support to be associated with risk of posttraumatic stress disorder (PTSD) symptoms among military personnel. While the lack of social support influences PTSD symptomatology, it is unknown how changes in perceived social support affect the PTSD symptom level in the aftermath of deployment. Furthermore, the influence of specific sources of social support from pre- to post-deployment on level of PTSD symptoms is unknown. We aim to examine how changes in perceived social support (overall and from specific sources) from pre- to 2.5 year post-deployment are associated with the level of post-deployment PTSD symptoms.

Methods

Danish army military personnel deployed to Afghanistan in 2009 and 2013 completed questionnaires at pre-deployment and at 2.5 year post-deployment measuring perceived social support and PTSD symptomatology and sample characteristics of the two cohorts. Data were analyzed using univariate and multivariate nominal logistic regression.

Results

Negative changes in perceived social support from pre- to post-deployment were associated with both moderate (OR 1.99, CI 1.51–2.57) and high levels (OR 2.71, CI 1.94–3.78) of PTSD symptoms 2.5 year post-deployment (adjusted analysis). Broadly, the same direction was found for specific sources of social support and level of PTSD symptoms. In the adjusted analyses, pre-deployment perceived social support and military rank moderated the associations.

Conclusions

Deterioration in perceived social support (overall and specific sources) from pre- to 2.5 year post-deployment increases the risk of an elevated level of PTSD symptoms 2.5 year post-deployment.