Effects of nitric oxide synthase inhibition on blood flow and survival in experimental skin flaps.

The aim of the present study was to examine the effect of the nitric oxide synthase (NOS) inhibitor N(omega)-nitro-l-arginine methyl ester (l-NAME) on skin and flap blood flow, NOS activity and flap survival in an ischaemic dorsal flap model in the rat. Fifty-four rats were used in the study. l-NAME or the inactive enantiomere d-NAME was given intravenously either pre-, per- and postoperatively or only postoperatively. Controls received saline treatment. Blood pressure and skin and flap blood flow were monitored. NOS activity was measured in intact skin before and after l-NAME and d-NAME infusion and in flap tissue 48h postoperatively. Forty-eight hours postoperatively flap survival was determined in all rats. l-NAME treatment caused: (1) a marked attenuation of constitutive Ca(2+) dependent NOS activity in intact skin (p<0.001), (2) an increase in blood pressure (p<0.05), (3) a decrease in blood flow in intact skin and in skin flaps (p<0.05), and (4) a decrease in flap survival (p<0.05). In saline and d-NAME treated animals no change in blood pressure, blood flow or NOS activity in intact skin was noted. In conclusion this study shows that l-NAME attenuates constitutive Ca(2+) dependent NOS activity in intact skin, decreases skin and flap blood flow and decreases the survival of skin flaps. These results indicate that constitutive nitric oxide synthase is important for basal blood flow in skin and flap tissue and for the survival of skin flaps.     

Multiple injections of coloured microspheres for islet blood flow measurements in anaesthetised rats: influence of microsphere size

We investigated if coloured microspheres could be used for repeated measurements of pancreatic islet blood flow in rats. An initial injection of 1.0-1.5 x 10(5) microspheres (black colour), with a size of 10 or 15 microm, was made into the ascending aorta, while an arterial reference sample was collected from the femoral artery. Twelve min later, 1 ml of saline or 30% D-glucose was injected intravenously. Three min after this injection a second injection of 10- or 15-microm microspheres (green colour) was given. The animals were then killed, and the pancreas and adrenals were removed and samples (150-200 mg) were secured from the duodenum, ileum, colon, right kidney and liver. The microsphere contents were determined with the aid of a freeze-thawing technique and blood flow values were calculated. Our results suggest that 10-microm microspheres, but not 15-microm microspheres, provide reproducible islet and total pancreatic blood flow measurements when repeatedly injected. Values for the blood flow to the intestines, kidney and liver were less sensitive to the size of the microspheres. We conclude that repeated administration of 15-microm microspheres induces a high risk for erroneous islet and total pancreatic blood flow measurements, whereas two such measurements can be performed if 10-microm microspheres are used.     

Prediction of large variation in biota to sediment accumulation factors due to concentration-dependent black carbon adsorption of planar hydrophobic organic compounds

Biota-to-sediment accumulation factors (BSAFs) sometimes show large variations between sites for a given planar hydrophobic organic compound (pHOC) in a given organism. We present a framework in which strong adsorption to soot/charcoal (black carbon [BC]) explains such BSAF variations. Recently constrained parameters on environmental BC sorption were used in a dual-mode sorption model of BSAE Variations in sedimentary BC content are shown to explain variations in BSAF of one to two orders of magnitude. In addition, strong BC sorption can explain the often-observed difference in BSAF between polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs). The strong nonlinearity of BC sorption can render BSAF values strongly concentration-dependent for a given sediment/organism/compound combination, so it is of paramount importance to carry out uptake and toxicity tests at the relevant environmental concentrations.     

A new biomedical sensor for measuring PCO2

Measuring PCO2 (partial pressure of carbon dioxide) in an organ can enable early detection of ischemia. However, there are few clinical applicable solutions for measuring PCO2. Based upon the requirement for clinical applications, a conductivity based PCO2 sensor is proposed. A conductivity based PCO2 sensor measures conductance in an aqueous solution separated from the measured object by a gas-permeable membrane. A bridge design with two cavities is favored for such a sensor. A planar and a cylindrical macro prototype based upon the bridge design were studied. The design criteria were based on the contribution from the electrode polarization, stray capacitances, contact area with the sample and design ability to miniaturize the sensor. The cylindrical sensor is favored because of its large contact area and advantages for miniaturization. Further investigation has to be done to confirm the functionality of such a design in a miniaturized form and its clinical performance.     

A novel infraclavicular brachial plexus block: the lateral and sagittal technique, developed by magnetic resonance imaging studies

A new infraclavicular brachial plexus block method has the patient supine with an adducted arm. The target is any of the three cords behind the pectoralis minor muscle. The point of needle insertion is the intersection between the clavicle and the coracoid process. The needle is advanced 0 degrees -30 degrees posterior, always strictly in the sagittal plane next to the coracoid process while abutting the antero-inferior edge of the clavicle. We tested the new method using magnetic resonance imaging (MRI) in 20 adult volunteers, without inserting a needle. Combining 2 simulated needle directions by 15 degrees posterior and 0 degrees in the images of the volunteers, at least one cord in 19 of 20 volunteers was contacted. This occurred within a needle depth of 6.5 cm. In the sagittal plane of the method the shortest depth to the pleura among all volunteers was 7.5 cm. The MRI study indicates that the new infraclavicular technique may be efficient in reaching a cord of the brachial plexus, often not demanding more than two needle directions. The risk of pneumothorax should be minimal because the needle is inserted no deeper than 6.5 cm. However, this needs to be confirmed by a clinical study. IMPLICATIONS: A new infraclavicular brachial plexus block method was investigated using magnetic resonance imaging without inserting needles in the volunteers. The study suggests two needle directions for performance of the block and that the risk of lung injury should be minimal. Expectations need to be confirmed by a clinical study.     

Use of antibiotics at hospitals in Stockholm: a benchmarking project using internet

PURPOSE: To evaluate the internet way of feedback to prescribing physicians, providing data on antimicrobial use and to assess the applicability of the DU90% (i.e. Drug Utilisation 90%--the number of drugs accounting for 90% of the volume of usage in defined daily doses, (DDDs)) methodology in the hospital setting. METHODS: Antimicrobial drug use was evaluated in all major departments in seven hospitals in Stockholm in the year 2000. All data were presented anonymously on www.janusinfo.org. Aggregate data on antimicrobial drug use were expressed as the number of DDDs and costs per 100 bed-days. We focused on the number of drugs accounting for 90% of the volume (DDD), including the level of adherence to guidelines. The chief physicians assessed this feedback by a questionnaire. RESULTS: The number of DDDs/100 bed-days varied among different clinics and ranged from 39 to 57 (internal medicine) to 102 to 161 (infectious disease). The cost per 100 bed-days varied more than two-fold. The number of different antibiotics within the DU90% segment ranged from 9 to 13 (orthopaedic clinics) to 16 to 23 (infectious disease). According to the questionnaire, data were considered to be clearly presented and physicians would like to receive this kind of reports in the future, not only for antibiotics but also for other drugs. CONCLUSION: Presenting physicians with aggregate data on drug use via internet could provide a stimulus for prescribing improvement.     

Metabolism of roquinimex in mouse and rat: an in vitro/in vivo comparison

1. In vitro studies with roquinimex, an immuno-modulator, in liver microsomes from mouse and rat were conducted to evaluate the primary metabolism and compare the metabolite pattern as well as the rate of metabolism with the in vivo pharmacokinetics of the compound in these two species. 2. In the presence of NADPH, roquinimex was metabolized to six primary metabolites (R1-6) by liver microsomes from mouse and rat. The formation of these metabolites was qualitatively similar in both species, and was greatly enhanced by pretreatment with PCN, an inducer of cytochrome P4503A. 3. The identification of the R1-6 demonstrated that roquinimex had been hydroxylated and demethylated. Hydroxylation at different sites of the quinoline moiety was the dominating reaction in both species. 4. Comparison of the resulting microsomal intrinsic clearance of 0.3 micromol mg(-1) protein min(-1) in mouse liver microsomes, versus 0.03 micromol mg(-1) protein min(-1) in rat liver microsomes demonstrated that the mouse possesses about a 10-fold greater metabolic capacity for roquinimex than the rat. 5. The in vivo pharmacokinetics of roquinimex demonstrated a 7-fold higher clearance in mouse than in the rat (82 ml h(-1) kg(-1) in mouse, 10.6 ml h(-1) kg(-1) in rat), which is in concordance with the in vitro findings.     

Impact of depressive mood on lifestyle changes in patients with coronary artery disease.

OBJECTIVE: The aims of this study were to investigate the time-course of depressive mood in patients with coronary artery disease during a secondary prevention rehabilitation program, and to analyse how different pre-treatment levels of depressive mood during a treatment phase were related to the degree of lifestyle change at 36 months follow-up. SUBJECTS: The study group comprised 109 of the original 183 consecutive coronary artery disease patients (91 male and 18 female) of whom 48 recently had experienced an acute myocardial infarction, 36 had been treated with coronary bypass surgery, 13 with percutaneous transluminal coronary angioplasty, and 12 had angina pectoris that had not been invasively treated. The subjects were divided into 3 subgroups based on their pre-treatment level of depressive mood. METHODS: Depressive mood was assessed at baseline, after 4 weeks and 12 months, using the depression subscale of the Hospital Anxiety and Depression scale. Lifestyle changes analysed included diet, smoking, relaxation (stress management) and exercise. RESULTS: Overall depressive mood ratings were significantly lower, both at the 4-week and 12-month assessments, compared with baseline, with the greatest improvements in patients with higher Hospital Anxiety and Depression measured depression. Original levels of depressive mood were not found to influence change of lifestyle habits during a 36-month follow-up period. CONCLUSION: Depressive mood might not be an obstacle to lifestyle changes when participating in a behaviourally oriented rehabilitation program including exercise-training, which might be a component important for improved depressive mood.     

Arousal modulation of memory and amygdala-parahippocampal connectivity: a PET-psychophysiology study in specific phobia

Phobic fear is accompanied by intense bodily responses modulated by the amygdala. An amygdala moderated psychophysiological measure related to arousal is electrodermal activity. We evaluated the contributions of electrodermal activity to amygdala-parahippocampal regional cerebral blood flow (rCBF) during phobic memory encoding in subjects with spider or snake phobia. Recognition memory was increased for phobia-related slides and covaried with rCBF in the amygdala and the parahippocampal gyrus. The covariation between parahippocampal rCBF and recognition was related to electrodermal activity suggesting that parahippocampal memory processes were associated with sympathetic activity. Electrodermal activity further mediated the amygdala effect on parahippocampal activity. Memory encoding during phobic fear therefore seems contingent on amygdala's influence on arousal and parahippocampal activity.