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.

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.

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.

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.

Low-dose bupivacaine with sufentanil prevents hypotension after spinal anesthesia for hip repair in elderly patients.

BACKGROUND: Hip fracture is common in the geriatric population. Patients in this group are often at high risk for perioperative complications from concurrent diseases. Conventional spinal anesthesia can be associated with hypotension but has a better postoperative outcome compared to general anesthesia. We judged that a reduced dose of bupivacaine in combination with sufentanil could give reliable blocks with minimal hypotension. METHODS: Fifty elderly patients were randomized into two groups. The study group received spinal anesthesia as a combination of hyperbaric bupivacaine 7.5 mg and sufentanil 5 microg while the control group received hyperbaric bupivacaine 15 mg. The hemodynamic stability of the patients and the quality of the blocks were compared. RESULTS: All patients had adequate duration of reliable blocks. More control group patients than study group patients required ephedrine due to hypotension. CONCLUSION: A reduced dose of hyperbaric bupivacaine (7.5 mg) in combination with sufentanil (5 microg) provides reliable spinal anesthesia for the repair of hip fracture in aged patients with few events of hypotension and little need for vasopressor support of blood pressure.

PCEA compared to continuous epidural infusion in an ultra-low-dose regimen for labor pain relief: a randomized study.

BACKGROUND: Patient-controlled epidural analgesia, PCEA, has been introduced in obstetric analgesia during the past decade. Many studies have shown that the consumption of analgesic is reduced when the parturient requests her own doses. This study investigates whether this is also true when using an ultra-low-dose regimen. METHODS: Eighty parturients were prospectively randomized to have either continuous epidural infusion (CEI) with ropivacaine 1 mg ml-1 and sufentanil 0.5 micro g ml-1, 6 ml h-1, or patient-controlled epidural analgesia (PCEA) with 4 ml demand doses with 20 min' lockout. The epidural start dose was the same for the two groups, 8 ml of the study solution. Rescue bolus doses were given when needed and the continuous infusion could be increased, which gave the two groups the same maximum possible dose. The consumption of local ropivacaine in combination with sufentanil during labor was registered. Hourly assessments made throughout labor included pain intensity documented with visual analog score, VAS, the patient's opinion on epidural efficacy, motor block, pruritus and need for nitrous oxide. RESULTS: The PCEA group consumed 33% less of the study solution than the CEI group. Mean total consumption was 35 ml (SD 18.0) and 52 ml (SD 19.6), respectively. Mean hourly consumption was 5.2 ml h-1 (SD 2.54) in the PCEA group and 6.9 ml h-1 (SD 1.31) in the CEI group. There were no significant differences between the two groups in pain relief, epidural efficacy, side-effects or obstetric outcome. CONCLUSION: PCEA reduces doses compared to continuous infusion even when ultra-low-dose local anesthetic with opioid is used. The PCEA technique provides individual titration of doses to an acceptable degree of pain relief.

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.

Parahydrogen-induced polarization in imaging: subsecond (13)C angiography.

High nuclear spin polarization of (13)C was reached in organic molecules. Enhancements of up to 10(4), compared to thermal polarization at 1.5 T, were achieved using the parahydrogen-induced polarization technique in combination with a field cycling method. While parahydrogen has no net polarization, it has a high spin order, which is retained when hydrogen is incorporated into another molecule by a chemical reaction. By subjecting this molecule to a sudden change of the external magnetic field, the spin order is transferred into net polarization. A (13)C angiogram of an animal was generated in less than a second. Magn Reson Med 46:1-5, 2001.

Cesarean section under epidural ropivacaine 0.75% in a parturient with severe pulmonary hypertension.

Pregnancy and delivery are a potentially lethal combination in a patient with primary pulmonary hypertension. There are controversies regarding mode of delivery. Cesarean section is considered to be associated with extensive perioperative risks. We report on a parturient with severe pulmonary hypertension who underwent a succesful semiemergent cesarean section on vital indication. Vaginal delivery was excluded since her cervix was too immature for succesful induction. This is the first reported case of its kind to receive an epidural anesthesia with ropivacaine with its potential advantage of a low cardiac toxicity. The epidural was slowly and carefully titrated to give a stable anesthesia with good quality.

Genotyping of the capsule gene cluster (cps) in nontypeable group B streptococci reveals two major cps allelic variants of serotypes III and VII.

Forty group B Streptococcus (GBS) isolates obtained from Europe and the United States previously reported to be nontypeable (NT) by capsule serotype determination were subjected to buoyant density gradient centrifugation. From nearly half of the isolates capsule-expressing variants could be selected. For characterization of the remaining NT-GBS isolates, the capsule operon (cps) was amplified by the long-fragment PCR technique and compared by restriction fragment length polymorphism (RFLP) analysis. The patterns from serotype reference isolates (n = 32) were first determined and used as a comparison matrix for the NT-GBS isolates. Using two restriction enzymes, SduI and AvaII, cluster analysis revealed a high degree of similarity within serotypes but less than 88% similarity between serotypes. However, serotypes III and VII were each split in two distant RFLP clusters, which were designated III(1) and III(2) and VII(1) and VII(2), respectively. Among the isolates that remained NT after repeated Percoll gradient selections, two insertional mutants were revealed. Both were found in blood isolates and harbored insertion sequence (IS) elements within cpsD: one harbored IS1548, and the other harbored IS861. All other NT-GBS isolates could, by cluster analysis, be referred to different serotypes by comparison to the RFLP reference matrix. In pulsed-field gel electrophoresis of SmaI-restricted chromosomal DNA, patterns from allelic type 1 and 2 isolates were essentially distributed in separate clusters in serotypes III and VII. A covariation with insertion sequence IS1548 in the hylB gene was suggested for serotype III, since allelic type III(1) harboring IS1548 in hylB, clustered separately. The variation in serotype VII was not dependent on the presence of IS1548, which was not detected at any position in the type VII chromosome.

A comparison of three doses of sufentanil in combination with bupivacaine-adrenaline in continuous epidural analgesia during labour.

BACKGROUND: Sufentanil is now frequently added to local anaesthetic in labour epidural analgesia. However, this opioid has some side effects such as pruritus, and in higher doses could harm the neonate. The purpose of this study was to compare three doses of sufentanil combined with low-dose bupivacaine, to determine the lowest appropriate dose. METHOD: In a prospective, randomized, double-blind study, 243 parturients were randomized, to receive A--0.5 microg/ml, or B--0.75 microg/ml or C--1 microg/ml sufentanil, in addition to bupivacaine 0.625 mg/ml+adrenaline 1.25 microg/ml. All were given an 8 ml bolus of the study solution, followed by continuous infusion at 6 ml/h. The analgetic effect was scored on a visual analogue scale (VAS). Onset quality was measured as VAS after 20 min, the total effect as VAS maximum during the first stage of labour. Overall maternal satisfaction was recorded within two hours post partum. Side effects were noted. RESULTS: There were no differences between groups in VAS assessments after 20 min or in maximum registered VAS. In group A, 83% had VAS 0-4 after 20 min, in group B 77% and in group C 71%. Maximum VAS during the first stage was 0-4 for 60% of group A, 68% of group B and 61% of group C. Maternal satisfaction was also the same in the three groups. In group A, 70% reported excellent effect and 22% good effect. The corresponding figures in group B were 68% and 24% respectively, and in group C 62% and 24% respectively. Group A received a mean total dose of 21 microg sufentanil, group B 30 microg and group C 44 microg. Pruritus occurred in 51% of group A, 53% of group B and 65% of group C. CONCLUSION: We found no difference in the analgesic effect between three different concentrations of sufentanil. We conclude that the lowest dose may be used. This should decrease the risk of adverse effects on mother and child.

Islet amyloid polypeptide in the islets of Langerhans: friend or foe?

Islet amyloid polypeptide (IAPP), or amylin, was originally discovered as the constituent peptide in amyloid occurring in human insulinomas and in pancreatic islets in human subjects with Type II (non-insulin-dependent) diabetes mellitus. Its normal expression in beta cells and its co-secretion with insulin in response to nutrient stimuli, suggest a metabolic function for the peptide. Specifically, IAPP has most frequently been shown to inhibit insulin secretion, implying that IAPP has a role in the regulation of islet hormone homeostasis. The physiological significance of IAPP in islets has been difficult to assess; very high IAPP concentrations are required to alter insulin secretion. Moreover, until recently, IAPP receptors have not been characterised at the molecular level, thus leaving the actual target cells for IAPP unidentified. Furthermore, in experimental diabetes in rodents, the ratio of IAPP expression to that of insulin invariably is increased. In view of the pleiotropic effects attributed to IAPP, such regulation could be both adverse and beneficial in diabetes. Metabolic characterisation of mice carrying a null mutation in the IAPP gene or which overexpress IAPP in beta cells have recently confirmed that IAPP is a physiological inhibitor of insulin secretion. Based on experiments in which IAPP-deficient mice develop a more severe form of alloxan-induced diabetes, we argue that the action of IAPP in the islets normally is beneficial for beta-cell function and survival; thus, the established up regulation of IAPP expression compared with that of insulin in experimental rodent diabetes could serve to protect islets under metabolically challenging circumstances.

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.

Clonal spread of staphylococci among patients with peritonitis associated with continuous ambulatory peritoneal dialysis.

BACKGROUND: Peritonitis is the most important complication of continuous ambulatory peritoneal dialysis (CAPD). Coagulase-negative staphylococci (CNS) are the most common causes of peritonitis, only limited information is available regarding the distribution and epidemiology of different CNS species associated with CAPD peritonitis. METHODS: CNS isolated from dialysis effluent from CAPD patients with peritonitis was identified by species and further analyzed with pulsed-field gel electrophoresis (PFGE). RESULTS: A total of 216 microorganisms (206 bacteria and 10 Candida species) were isolated from 196 consecutive culture-positive CAPD samples obtained from 75 patients. One hundred and twenty-one (56%) isolates represented staphylococci. The four most frequently isolated staphylococcal species were Staphylococcus epidermidis (70 isolates), Staphylococcus aureus (31 isolates), Staphylococcus hemolyticus (10 isolates), and Staphylococcus hominis (4 isolates). PFGE analysis revealed the clonal spread among patients of three different clones of S. epidermidis and one clone of S. aureus among the investigated patients. Indistinguishable isolates of either S. epidermidis, S. hominis, or S. aureus were also isolated in repeated samples from several patients. CONCLUSION: PFGE is a useful method for the epidemiological evaluation of staphylococci-associated CAPD infections and should replace older and less accurate methods, such as antibiotic sensitivity patterns. We recommend that CNS isolates from patients with CAPD-associated peritonitis should be saved for future investigations and typing, which would aid in the management of this patient category.

Antibiotic susceptibility of staphylococci isolated in blood cultures in relation to antibiotic consumption in hospital wards.

A total of 510 isolates of Micrococcaceae, 500 of staphylococci and 10 micrococci, detected in 485 (3.3%) of 14,860 consecutive blood cultures obtained from patients at a Swedish university hospital and 2 local hospitals were identified to species level and investigated for antibiotic susceptibility. The 5 most frequently isolated species were Staphylococcus epidermidis (54.8%), S. aureus (28.0%), S. hominis (3.4%), S. warneri (3.2%) and S. haemolyticus (2.8%). All isolates of S. aureus were oxacillin sensitive. Great diversity in antibiotic resistance among coagulase negative staphylococci between hospitals and different ward units in the university hospital was observed. The frequency of antimicrobial resistance among S. epidermidis correlated with the antibiotic consumption at different ward units, in particular for ciprofloxacin (p < 0.001) and co-trimoxazole (p < 0.004). The study emphasizes the importance of monitoring antibiotic consumption and resistance patterns of nosocomial staphylococci in order to avoid emergence and spread of multi-resistant bacteria within the hospital environment.

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.

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.