Laser Wakefield Driven Generation of Isolated Carrier-Envelope-Phase Tunable Intense Subcycle Pulses.

Sources of intense, ultrashort electromagnetic pulses enable applications such as attosecond pulse generation, control of electron motion in solids, and the observation of reaction dynamics at the electronic level. For such applications, both high intensity and carrier-envelope-phase (CEP) tunability are beneficial, yet hard to obtain with current methods. In this Letter, we present a new scheme for generation of isolated CEP tunable intense subcycle pulses with central frequencies that range from the midinfrared to the ultraviolet. It utilizes an intense laser pulse that drives a wake in a plasma, copropagating with a long-wavelength seed pulse. The moving electron density spike of the wake amplifies the seed and forms a subcycle pulse. Controlling the CEP of the seed pulse or the delay between driver and seed leads to CEP tunability, while frequency tunability can be achieved by adjusting the laser and plasma parameters. Our 2D and 3D particle-in-cell simulations predict laser-to-subcycle-pulse conversion efficiencies up to 1%, resulting in relativistically intense subcycle pulses.

Plasma concentration of ketorolac after local infiltration analgesia in hip arthroplasty.

BACKGROUND: Local infiltration analgesia (LIA) with local anaesthetic (ropivacaine), a nonsteroidal anti-inflammatory drug (ketorolac) and epinephrine after lower extremity arthroplasty has gained increasing popularity during the last decade. This method has certain advantages, which include minimal systemic side effects, faster post-operative mobilization, earlier post-operative discharge from hospital and less opioid consumption. However, information regarding plasma concentrations of ketorolac after LIA mixture is insufficient to predict the risk of renal impairment in patients subjected to arthroplasty. AIM: To determine the maximal plasma concentration and the exposure of ketorolac during the first 30 h following LIA in hip arthroplasty. METHODS: Thirteen patients scheduled for primary total hip arthroplasty with LIA (ropivacaine 200 mg, ketorolac 30 mg and epinephrine 0.5 mg in a volume of 106 ml) were included. Plasma concentration of ketorolac was quantified by liquid chromatography-mass spectrometry. In addition, we assessed the effect of increasing age and decreasing glomerular filtration rate on the maximal plasma concentration and the total exposure to ketorolac during 30 h. RESULTS: The range of the maximal plasma concentration, 0.3-2.2 mg/l, was detected 30 min-4 h after completing the infiltration. Similar plasma levels have been reported after intramuscular injection of the same dose of ketorolac to healthy elderly volunteers. CONCLUSION: Exposure to ketorolac after LIA may be comparable to an intramuscular injection of the same dose. Decision of dose reduction should be based on clinical assessment of risk factors.

A randomized, single-blind, increasing dose safety trial of an oxygen-carrying plasma expander (Hemospan) administered to orthopaedic surgery patients with spinal anaesthesia.

The objective of this study was to further explore the safety of Hemospan (Sangart Inc., San Diego, CA, USA), an oxygen-carrying plasma expander. The aim of this study was to determine if Hemospan is well tolerated in orthopaedic surgery patients with spinal anaesthesia in doses up to 1 L. Hemospan was previously found to be well tolerated in normal volunteers and orthopaedic surgery patients with spinal anaesthesia in doses up to 500 mL. Five cohorts of six orthopaedic surgery patients, American Society of Anesthesiologists (ASA) I and II, were studied. In each cohort, four patients received Hemospan in doses ranging from 200 to 1000 mL, and two received Ringer's lactate immediately prior to induction of spinal anaesthesia. There were no serious adverse events (SAEs). Iohexol clearance measured before and 24 h after dosing was unaffected. There were 14 adverse events (AEs) in the 10 control patients (1.4 per patient) and 30 in the 20 patients receiving Hemospan (1.5 per patient). One patient in the group receiving 200 mL Hemospan had elevated mean arterial pressure after dosing, but there were no elevations in any of the other patients. The peak plasma Hemospan concentration in the 1000 mL group was 1.3 g dL(-1), with a dose-dependent clearance (T(1/2)) ranging from 14.1 to 23.0 h. Plasma methaemoglobin levels were independent of dose, reaching a maximum at 40 h after dosing and never exceeded 0.125 g dL(-1). Troponin T was transiently elevated in two patients receiving Hemospan without symptoms or electrocardiographic abnormalities or elevation of myocardial creatinine kinase isoenzyme. Hemospan was well tolerated in this group of patients at doses up to 1000 mL.

Postantibiotic effect and postantibiotic sub-mic effect of dirithromycin and erythromycin against respiratory tract pathogenic bacteria.

The postantibiotic effect (PAE) of dirithromycin and erythromycin against strains Streptococcus pyogenes group A M12, NCTC P1800, Streptococcus pneumoniae 23, Staphylococcus aureus Oxford strain 209, Moraxella catarrhalis 15616 and Haemophilus influenzae 5590 was investigated in vitro and in vivo by use of the tissue cage model in rabbits. By exposing strains to 2.5-5 x MIC levels for 6 h or 12 h, both compounds induced in vitro PAEs of 1-9 h, and in two cases >20 h. Cultures in the PAE-phase were then re-exposed to subinhibitory concentrations (0.25 x MIC and 0.5 x MIC) of antibiotic and prolonged suppression of regrowth was obtained for 2->20 h. Following i.v. antibiotic treatment of rabbits (10 mg/kg or 20 mg/kg dirithromycin and 20 mg/kg or 40 mg/kg erythromycin) and bacterial infection of the implanted tissue cages in the same rabbit, the tissue cage fluid (TCF) was sampled 6 h after infection and regrowth was monitored by sampling from new tissue cages in untreated rabbits. These i.v. single doses of both antibiotics induced in vivo PAEs of >6 h, but <20 h against S. pyogenes. Suppression of regrowth in TCF was also obtained for > or = 20 h on infection with exposed S. pyogenes in the PAE-phase in newly implanted tissue cages in rabbits that had been treated with low doses of antibiotic to produce subinhibitory concentrations in the TCE Dirithromycin was in general as active as erythromycin in inducing PAE and in prolonging suppression of bacterial regrowth in the PAE phase.

Increased cerebrospinal fluid concentration of aspartate but decreased concentration of nitric oxide breakdown products in women experiencing visceral pain during active labour.

The aim of the present study was to investigate some putative neurotransmitters involved in nociception and pain in parturients during active labour experiencing intense visceral pain. The concentration of the excitatory amino acid aspartate was significantly increased, and there was a tendency for an increase in glutamate, in lumbar cerebrospinal fluid (CSF) of parturients in active vaginal labour compared with control patients without pain subjected to elective caesarean section. The CSF concentration of the nitric oxide breakdown product nitrate was significantly decreased in parturients compared with control patients and healthy volunteers. No significant differences in the concentrations of substance P, substance P-endopeptidase or met-enkephalin were detected between parturients and controls. Our data suggest a paradoxical negative relationship between CSF concentrations of excitatory amino acids and nitric oxide in labour pain. The mechanisms behind this finding is unclear at present.

A preliminary evaluation of a new selective agar supplemented with desferrioxamine for detection of methicillin-resistant Staphylococcus aureus.

The aim of the present study was to evaluate the performance of two new selective screening agars, Colombia agar supplemented with 1000 mg/L desferrioxamine, 5 mg/L amphotericin B, 16 mg/L polymyxin B, and 2 mg/L methicillin (CMDAP agar) or 0.5 mg/L oxacillin (CODAP agar), for detection of methicillin-resistant Staphylococcus aureus (MRSA). Both the CMDAP and the CODAP agar effectively inhibited growth of 151 isolates of coagulase-negative staphylococci (CoNS), 45 of Enterobacteriaceae and six Candida spp. examined. The sensitivity and specificity of the CMDAP and CODAP agars for detection of MRSA was calculated by comparing the growth of 52 MRSA with the inhibition of 74 mecA negative S. aureus and of 151 CoNS. The performance of the new agars was compared with four previously described MRSA screening agars. The sensitivity and specificity for detection of MRSA after incubation at 35 degrees C for 24 h was 0.94 and 0.91, respectively, for the CMDAP agar, 0.60 and 0.90 for the CODAP agar, 0.98 and 0.57 for methicillin aztreonam mannitol salt agar (MAMSA), 0.23 and 0.84 for oxacillin mannitol salt agar (OMSA), 0.48 and 0.76 for oxacillin Mueller-Hinton agar (OMHA) and 0.75 and 0.77 for lithium oxacillin mannitol salt agar (LOMSA). Agars supplemented with desferrioxamine, CMDAP and CODAP, were more specific for detecting MRSA compared with agars not supplemented with desferrioxamine. The detection rate was higher for agars supplemented with methicillin than for agars supplemented with oxacillin.

Intracranial subdural haematoma complicates accidental dural tap during labour.

A 19-year-old, healthy nulliparous woman developed an intracranial subdural haematoma after unintentional dural puncture in connection with epidural analgesia for labour pain. The haematoma was evacuated and the patient recovered completely. Anaesthesiologists and obstetricians should be aware of this rare but potentially dangerous complication to epidural analgesia.

Post-partum urinary retention: a comparison between two methods of epidural analgesia.

OBJECTIVE: To compare two methods of epidural labor analgesia regarding the incidence of post-partum urinary retention. STUDY DESIGN: One thousand parturients who requested epidural analgesia for the relief of labor pain received, at random, either bupivacaine 0.25% with adrenaline 1:200 000 (n = 500) or bupivacaine 0.125% with 10 micrograms sufentanil (n = 500). During the same observation period all women with clinically significant urinary retention (> 500 ml, requiring indwelling catheter) were registered. RESULT: Altogether 30/3.364 parturients had clinically significant urinary retention. Twenty-seven of these had received epidural analgesia (EDA) (17 with bupivacaine/adrenaline and ten with bupivacaine/sufentanil, a non-significant differences). The number of parturients with urinary retention was highly increased following EDA (27/1000) as compared to those not receiving EDA (3/2364), P < 0.001 (Fisher's exact test). In patients with EDA and urinary retention there were no difference between the groups in the incidence of instrumental deliveries or vaginal/perirectal tears. All parturients regained normal bladder function. CONCLUSION: EDA significantly increased the risk of post-partum urinary retention but no difference was found between the two epidural techniques.

Diclofenac in the treatment of pain after caesarean delivery. An opioid-saving strategy.

OBJECTIVE: Pain relief of good quality after caesarean section (CS) results in early mobilization and good early mother-child interaction. Patient-controlled analgesia (PCA), with systemic opioids, gives a very high level of patient satisfaction. However, opioids have well documented side-effects i.e. sedation, nausea and respiratory depression. To minimize the risk of such negative effects we studied how far the required dose of opioid could be decreased with a multimodal strategy adding diclofenac. STUDY DESIGN: In a randomized double-blind study, 50 parturients scheduled for elective CS under spinal anaesthesia, received rectally either diclofenac (Suppositorium diclofenac) 50 mgx3 or placebo 1x3 during the first 24 h postoperatively. All patients had PCA with the possibility of self-administered doses of ketobemidone 1 mg/6 min. RESULTS: In the group receiving diclofenac rectally the consumption of ketobemidone was reduced with 39% compared to the placebo group. CONCLUSION: A multimodal analgetic strategy with the addition of 150 mg diclofenac during the first 24 h after CS reduces the need for opioids significantly with maintained or improved analgetic effect. This is expected to reduce the risk of negative side-effects of systemic opioids.

In vitro inhibition of S. pneumoniae, nontypable H. influenzae and M. catharralis by alpha-hemolytic streptococci from healthy children.

The present study aimed to investigate the inhibitory activity of the normal epipharyngeal flora against the three most common acute otitis media (AOM) pathogens in healthy children, and to study if the inhibitory activity differs between alpha-hemolytic streptococci (AHS) sampled from the tubal orifice and from those sampled from the adenoid. A total number of ten isolates of AHS were collected from the tubal orifice and the adenoid, respectively, in ten children undergoing adenoidectomy or tonsillectomy. None of the children had a history of otitis media, neither secretory otitis media (SOM) nor AOM. The method used to test the bacterial interference in vitro was a modified agar overlay method. The results showed that the AHS from nasopharynx were able to inhibit the majority of the S. pneumoniae, nontypable Haemophilus influenzae and Moraxella catharralis isolates tested. The AHS isolates from the tubal orifice inhibited growth of 93% of S. pneumoniae, 79% of H. influenzae and 84% of M. catharralis isolates. The corresponding figures among isolates from the adenoid were 76, 48 and 62%. This difference in the inhibitory capacity between the AHS isolates collected from the adenoid, compared with the AHS collected from the tubal orifice, is statistically significant (P<0.01) and implies that it is important to know the exact sampling locality before conclusions are made concerning the significance of bacterial interference in the upper airways.

Analgesic efficacy of intravenous morphine in labour pain: a reappraisal.

The aim of the present study was to investigate the dose-related analgesic effect of intravenous (i.v.) morphine during spontaneous term first stage labour. This was an open study in 17 parturients who requested analgesia for severe labour pain. All women were given morphine i.v. in repeated doses of 0.05 mg/kg following every third contraction until a final dose of 0.20 mg/kg was reached. The decrease in overall pain intensity, from median visual analogue scale (VAS) 85 (range 52-100) to median VAS 70 (range 46-99), was clinically insignificant. The number of women experiencing back pain, however, decreased significantly following morphine. The most striking effect of morphine (7.2-18 mg) was pronounced sedation. No adverse reactions related to morphine were noted in the neonates. We conclude that i.v. morphine does not significantly reduce overall labour pain intensity. Thus, if a real analgesic effect is desired, systemically given morphine seems inappropriate and other techniques should be used.

Long-term exposure of mouse pancreatic islets to oleate or palmitate results in reduced glucose-induced somatostatin and oversecretion of glucagon.

AIMS/HYPOTHESIS: Long-term exposure to NEFAs leads to inhibition of glucose-induced insulin secretion. We tested whether the release of somatostatin and glucagon, the two other major islet hormones, is also affected. METHODS: Mouse pancreatic islets were cultured for 72 h at 4.5 or 15 mmol/l glucose with or without 0.5 mmol/l oleate or palmitate. The release of glucagon and somatostatin during subsequent 1 h incubations at 1 or 20 mmol/l glucose as well as the islet content of the two hormones were determined. Lipid-induced changes in islet cell ultrastructure were assessed by electron microscopy. RESULTS: Culture at 15 mmol/l glucose increased islet glucagon content by approximately 50% relative to that observed following culture at 4.5 mmol/l glucose. Inclusion of oleate or palmitate reduced islet glucagon content by 25% (at 4.5 mmol/l glucose) to 50% (at 15 mmol/l glucose). Long-term exposure to the NEFA increased glucagon secretion at 1 mmol/l glucose by 50% (when islets had been cultured at 15 mmol/l glucose) to 100% (with 4.5 mmol/l glucose in the culture medium) and abolished the inhibitory effect of 20 mmol/l glucose on glucagon secretion. Somatostatin content was unaffected by glucose and lipids, but glucose-induced somatostatin secretion was reduced by approximately 50% following long-term exposure to either of the NEFA, regardless of whether the culture medium contained 4.5 or 15 mmol/l glucose. Ultrastructural evidence of lipid deposition was seen in <10% of non-beta cells but in >80% of the beta cells. CONCLUSIONS/INTERPRETATION: Long-term exposure to high glucose and/or NEFA affects the release of somatostatin and glucagon. The effects on glucagon secretion are very pronounced and in type 2 diabetes in vivo may aggravate the hyperglycaemic effects due to lack of insulin.

Analgesic efficacy of diclofenac in combination with morphine and paracetamol after mastectomy and immediate breast reconstruction.

BACKGROUND: Breast cancer treatment with mastectomy and immediate breast reconstruction (IBR) is associated with intense pain in the primary post-operative period. The present prospective, placebo-controlled and double-blind study aimed to evaluate the analgesic efficacy of diclofenac, a non-steroid anti-inflammatory drug (NSAID), in combination with paracetamol and opioids. This was done by 64-h assessment of post-operative pain intensity, opioid consumption, blood loss, nausea and tiredness. METHODS: Fifty women selected for mastectomy and IBR with submuscular implants with or without axillary lymph node dissection (ALND) were randomized to receive diclofenac 50 mg x 3 or placebo rectally in addition to oral paracetamol and intravenous opioids delivered using a patient-controlled analgesia (PCA) technique. RESULTS: During the first 20 h post-surgery, patients who received diclofenac experienced significantly less pain when resting than those who received placebo. When moving, a non-significant estimated difference in pain in favour of diclofenac was also noted. Opioid consumption during the first 6 h post-operatively was 34% less with diclofenac than with placebo. Means (SD) were 16.9 (10.3) mg and 25.6 (10.2) mg, respectively (P = 0.007). After 64 h, the difference was no longer statistically significant. Post-operative bleeding was significantly higher with diclofenac than with placebo (P < 0.01). Nausea and tiredness did not differ between the groups. CONCLUSIONS: The addition of NSAID to paracetamol and opioid-PCA reduced opioid consumption and improved pain relief during the first 20 h at rest but was not convincingly effective during mobilization. Post-operative blood loss was higher with diclofenac.

Traditional analgesic agents: are parenteral narcotics passé and do inhalational agents still have a place in labour?

Systemic labour pain treatment with opioids and inhaled nitrous oxide has for many decades frequently been used in medically developed countries. Self-administered nitrous oxide (50% in oxygen) has never gained the same popularity in the USA as in the UK or Scandinavia but the use of opioids, mainly pethidine, has generally been widespread in spite of well-known negative effects on the postnatal adaptation of the newborn. Since the often very intense labour pain seems to respond very poorly even to highly sedating doses of parenteral opioids, their frequent use during delivery and parturition has to be questioned. Self-administered inhalation of nitrous oxide 50% in oxygen also has a limited efficacy for relieving labour pain but because it is mainly devoid of adverse effects on the baby or on the parturient its future use in obstetrics can be defended more easily, either as a sole agent in women with low labour pain scores or in early labour preceding epidural analgesia.

Drugs up in smoke: a study of caseated drugs in Sweden.

DESIGN: Cross-sectional survey. SETTING: The county of Malmöhus, with 817,000 inhabitants, in the far south of Sweden. All drugs handed in for destruction to the 65 pharmacies during one week in March 1996 were analysed. RESULTS: 92% of the packages were prescription drugs for human use, 7% were over-the-counter drugs, and 1% were for veterinary use. Slightly less than half (48%) had expired when they were handed in for destruction. 36% were unbroken when returned and another 18% of the packages were nearly full. A comparison between the drugs sent in for destruction and the drugs sold in the county gave a ratio of 0.030. Antineoplastic and immunosuppressive drugs, drugs for the respiratory system, antiparasitic products, and cardiovascular drugs were returned to a greater extent than other types of drugs. Drugs for the genito-urinary tract, sex hormones, and drugs for the alimentary tract were returned to a lesser extent. Extrapolated to a whole year the value of caseated drugs was estimated to 60 SEK (5.83 Br,) per person. The value of unbroken packages was 20 SEK (1.94 Br,) per person per year. CONCLUSION: Although not all of the drugs handed in for destruction could have been unnecessarily prescribed or obtained by the patient, a more cautious approach to prescribing of drugs would likely yield significant savings.

One-trial learning and superior resistance to extinction of autonomic responses conditioned to potentially phobic stimuli.

Human subjects were exposed to pictures of potentially phobic (snakes) and supposedly neutral (houses) objects as conditioned stimuli (CSs) in a Pavlovian conditioning experiment with shock as unconditioned stimulus (US), and skin conductance and finger pulse volume as dependent variables. The skin conductance responses conditioned to phobic stimuli were acquired after one CS-US pairing, and showed practically no extinction, whereas the responses to neutral stimuli showed very little resistance to extinction after both 1 and 5 reinforcements. The superior resistance to extinction of the phobic condition was interpreted to be a specific associative effect. In general, the skin conductance acquisition data showed tendencies similar to those during extinction. For finger pulse volume responses, however, there were very weak conditioning effects, and no effect of stimulus.