Effect of epidural analgesia with ambulation on labor duration.

BACKGROUND: Ambulatory epidural analgesia (AEA) is a popular choice for labor analgesia because ambulation reportedly increases maternal comfort, increases the intensity of uterine contractions, avoids inferior vena cava compression, facilitates fetal head descent, and relaxes the pelvic musculature, all of which can shorten labor. However, the preponderance of evidence suggests that ambulation during labor is not associated with these benefits. The purpose of this study is to determine whether ambulation with AEA decreases labor duration from the time of epidural insertion to complete cervical dilatation. METHODS: In this prospective, randomized study, 160 nulliparous women with AFA were randomly assigned to one of two groups: AEA with ambulation and AEA without ambulation. AEA blocks were initiated with 15-20 ml ropivacaine (0.07%) plus 100 microg fentanyl, followed by a continuous infusion of 0.07% ropivacaine plus 2 microg/ml fentanyl at 15-20 ml/h. Maternal measured variables included ambulation time, time from epidural insertion to complete dilatation, stage II duration, pain Visual Analogue Scale scores, and mode of delivery. APGAR scores were recorded at 1 and 5 min. Results are expressed as mean +/- SD or median and analyzed using the t test, chi-square, or the Mann-Whitney test at P < or = 0.05. RESULTS: The ambulatory group walked 25.0 +/- 23.3 min, sat upright 40.3 +/- 29.7 min, or both. Time from epidural insertion to complete dilatation was 240.9 +/- 146.1 min in the ambulatory group and 211.9 +/- 133.9 min in the nonambulatory group (P = 0.206). CONCLUSION: Ambulatory epidural analgesia with walking or sitting does not shorten labor duration from the time of epidural insertion to complete cervical dilatation.

Uptake, transport, and delivery of antimicrobial agents by human polymorphonuclear neutrophils.

Polymorphonuclear neutrophils (PMN) are attracted to sites of infection. They have the potential to deliver antimicrobial agents to these sites if the agents enter the cells and do not alter migration. Penicillin G did not enter cells and was not transported by PMN. We found that azithromycin, ciprofloxacin, levofloxacin, moxifloxacin, and telithromycin were concentrated in PMN and transported toward a chemoattractant. These antimicrobial agents were released from the PMN and inhibited the growth of bacteria on test plates.

Adequacy of fellowship training: results of a survey of recently graduated fellows.

The adequacy of fellowship training in the field of infectious diseases was assessed by means of a survey of recently graduated fellows. Surveys were mailed to all individuals who had passed the American Board of Internal Medicine's board certification examination in infectious diseases since 1992. A total of 666 completed surveys were returned by the deadline (response rate, 36%). Although most recent graduates thought that training in the standard components of clinical infectious diseases was adequate, only 50% thought that training in infection control was adequate. Fewer than 1 in 3 believed that they had received adequate training in the business aspects of infectious diseases practice. The adequacy and duration of research training were linked to ultimate career choice. These results form the basis for the Infectious Diseases Society of America's new initiatives to assist with more-diversified and relevant fellowship training.

Postdural puncture headache: a randomized comparison of five spinal needles in obstetric patients.

This prospective, blinded, randomized study compares the incidence of postdural puncture headache (PDPH) and the epidural blood patch (EBP) rate for five spinal needles when used in obstetric patients. One thousand two women undergoing elective cesarean delivery under spinal anesthesia were recruited. We used two cutting needles: 26-gauge Atraucan and 25-gauge Quincke, and three pencil-point needles: 24-gauge Gertie Marx (GM), 24-gauge Sprotte, and 25-gauge Whitacre. The needle for each weekday was chosen randomly. Cutting needles were inserted parallel to the dural fibers. The incidences of PDPH were, respectively, 5%, 8.7%, 4%, 2.8%, and 3.1% for Atraucan, Quincke, GM, Sprotte, and Whitacre needles (P = 0.04, chi(2) analysis), and the corresponding EBP rates in those with PDPH were 55%, 66%, 12.5%, 0%, and 0% (P = 0.000). The Quincke needle had a more frequent PDPH rate than the Sprotte or the Whitacre needle (P = 0.02) and a more frequent EBP rate than the GM, Sprotte, or the Whitacre needle (P = 0.01). The Atraucan needle had a more frequent EBP rate than the Sprotte or Whitacre needle (P = 0.05). Neither the PDPH rate nor the EBP rates differed among the pencil-point needles. The cost of EBP must be taken into consideration when choosing a spinal needle. We conclude that pencil-point spinal needles should be used for subarachnoid anesthesia in obstetric patients.

Activities of antimicrobial agents against intracellular pneumococci.

Pneumococci can enter and survive inside human lung alveolar carcinoma cells. We examined the activity of azithromycin, gentamicin, levofloxacin, moxifloxacin, penicillin G, rifampin, telithromycin, and trovafloxacin against pneumococci inside and outside cells. We found that moxifloxacin, trovafloxacin, and telithromycin were the most active, but only telithromycin killed all intracellular organisms.

Uniport soft-tip, open-ended catheters versus multiport firm-tipped close-ended catheters for epidural labor analgesia: a quality assurance study.

STUDY OBJECTIVE: To compare a multiport, firm-tipped, close-ended, epidural catheter (Portex catheter) with a uniport, open-ended, soft-tipped, wire-reinforced catheter (Arrow catheter) in obstetric patients. STUDY DESIGN: Prospective data collection for intradepartmental quality assurance. SETTING: Obstetric unit in a tertiary care maternity hospital. PATIENTS: 2612 patients requesting labor analgesia. INTERVENTIONS: The Arrow catheter was used in 1,352 women and the Portex catheter in 1,260 women. MEASUREMENTS AND MAIN RESULTS: The incidence of unsatisfactory block were 3.3% and 4.4% with the Arrow and Portex catheters, respectively (p = 0.2). The catheter perforated the dura matter in 0.4% of cases with both catheters. The incidence of epidural venipuncture was 1.1% with the Arrow catheter and 5.7% with the Portex catheter (p = 0.0001). Paresthesias occurred in 6% of cases with the Arrow catheter and 11. 2 % of cases with the Portex catheter (p = 0.0001). Epidural catheter reinsertion was required in fewer patients in the Arrow group than in the Portex group (4.8% vs. 7.1%; p = 0.01). CONCLUSIONS: In obstetric patients, the softer uniport Arrow catheter produces paresthesias and venipunctures less frequently than the firm multiport Portex catheter.

Post partum creatine phosphokinase and its muscle-brain isoenzyme elevation and transient Q-wave in a patient with idiopathic hypertrophic subaortic stenosis.

A primigravida with idiopathic hypertrophic subaortic stenosis, New York Heart Association Classification III, developed acute chest pain with significant ST segment depression together with a new Q-wave in chest lead V6 on the electrocardiograph following delivery under lumbar epidural analgesia. An intrapartum myocardial infarct was suspected because serial creatine phosphokinase and its muscle-brain isoenzyme levels were elevated in the postpartum period. However, the ST segment and the Q-wave changes returned to baseline within 4 h, thus eliminating the possibility of acute myocardial infarction. The uterus and placenta release creatine phosphokinase and its muscle-brain isoenzyme substantially during normal vaginal delivery, thus mimicking acute myocardial infarction. Consequently, the elevations of creatine phosphokinase and its muscle-brain fraction alone are not diagnostic of myocardial infarction in the postpartum period. The diagnosis of myocardial infarction must be based on the clinical picture, serial electrocardiogram recording and determination of lactate dehydrogenase and aspartate amino transferase.

Fellowship training in infectious diseases: a report from the regional and national meetings of infectious diseases division chiefs and program directors.

During the 2-year period April 1995 to April 1997, six regional meetings and one national meeting of division chiefs and program directors of adult infectious diseases programs in the United States were held to review fellowship training. Herein, we report data on job availability and job selection for recently graduated fellows. We summarize discussions on decreasing the number of fellows in training, and we outline suggested components of a core clinical curriculum and of three training tracks--clinician track, clinical investigator track, and basic investigator track.

The new antibiotics, 1997.

Some of the antimicrobial agents released in the past few years possess characteristics suggesting real advantages over older agents (see Table I). These advantages include broader spectrum of activity, favorable pharmacokinetic profile allowing for infrequent dosing, low toxicity and lower pricing. Although older agents and agents with narrower spectra should be considered first-line in most circumstances, there may be some clinical scenarios in which these newer agents should be contemplated as reasonable alternatives.

Interaction of tumor necrosis factor-alpha and granulocyte colony-stimulating factor on neutrophil apoptosis, receptor expression, and bactericidal function.

Infected patients are likely to have increased levels of tumor necrosis factor-alpha (TNF-alpha) and may be treated with recombinant human granulocyte colony-stimulating factor (G-CSF). Recombinant human TNF-alpha activates polymorphonuclear neutrophil (PMN) inflammatory activity. We examined the effect of exposure to TNF-alpha and G-CSF alone and in combination on PMN apoptosis, receptor expression, phagocytosis, and bactericidal function. The results were compared to those obtained with a promoter of PMN apoptosis, cycloheximide. After 24 hr, 27% of PMNs were nonapoptotic, and TNF-alpha (1 unit/ml) showed no change. Cycloheximide (10 micrograms/ml) decreased the number of nonapoptotic cells to 10% of the initial PMN. In contrast, G-CSF (30 ng/ml) decreased apoptosis (57% nonapoptotic PMN after 24 hr). Both G-CSF and TNF-alpha (but not cycloheximide) induced preservation of PMN Fc gamma RIII (467% and 167% of 24-hr controls, respectively) and beta 2-integrin expression (150% and 168% of 24-hr controls, respectively). G-CSF (but not TNF-alpha or cycloheximide) stimulated expression of Fc gamma RI (191% of 24-hr control) and Fc gamma RII (267% of 24-hr control). G-CSF (but not TNF-alpha) maintained the ability of PMN to ingest and kill opsonized Staphylococcus aureus. TNF-alpha decreased the effect of G-CSF on apoptosis, expression of Fc gamma RIII and Fc gamma RI, and bactericidal function. Thus, TNF-alpha promoted expression of Fc gamma RIII and beta 2-integrin receptors, which are important for phagocytic activity, and G-CSF diminished apoptosis, increased Fc gamma receptor expression, and maintained bactericidal function. TNF-alpha counteracted some effects of G-CSF. Interactions of these cytokines in vivo serve to regulate the PMN inflammatory response and bactericidal capacity.

Hemodynamic effects of subarachnoid fentanyl in laboring parturients.

BACKGROUND AND OBJECTIVES: The subarachnoid administration of fentanyl to laboring parturients may decrease maternal blood pressure. The hemodynamic effects of subarachnoid fentanyl (SAF) in laboring women was studied by impedance cardiography. METHODS: Following a 500 mL fluid bolus, 15 healthy women received 25 micrograms of SAF for labor analgesia by a combined spinal-epidural technique. Maternal systolic, mean, and diastolic blood pressure, heart rate, cardiac index, stroke index, and end-diastolic index were measured before SAF administration (baseline) and every 5 minutes for 30 minutes after administration. Prelabor blood pressure values were obtained from the patient's last office visit. Data were analyzed by analysis of variance at P < .05. RESULTS: Following SAF administration, pain scores decreased and pruritus scores increased (based on 100-mm visual analog scales). Maternal systolic, diastolic, and mean blood pressures, heart rate, and cardiac index decreased significantly by 12, 18, 17, 12, and 14%, respectively, as compared with baseline values, with no significant change in stroke index. Cardiac preload (end-diastolic index) decreased by 10% 25 minutes following SAF administration but otherwise did not significantly change. Compared with prelabor blood pressure values, the diastolic pressure decreased significantly only 9% at 20 minutes and the mean arterial pressure decreased only 7 and 8% at 20 and 25 minutes, respectively; the systolic pressure did not change. In 53% of patients, at least one hypotensive episode (systolic pressure of < or = 100 mm Hg or a > 30% decrease in systolic pressure) occurred, following SAF administration. However, only two of these episodes (systolic pressures of 93 and 96 mm Hg) lasted longer than 1 minute, and these were easily treated with intravenous ephedrine. CONCLUSIONS: Vasodilation due to sympathectomy causes a decrease in preload (end-diastolic index) and in stroke index and an increase in heart rate. Since the end-diastolic index and stroke index remained relatively stable and the heart rate decreased, it was concluded that the observed decrease in blood pressure was not due to vasodilation.

The role of molecular techniques in the understanding of emerging infections.

Emerging infections are defined as infections that are newly identified or recognized, or those whose incidence in humans has significantly increased over the past 20 years. The interaction of several factors contributes to the emergence of infectious disease, including changes in human behavior, technological advances, economic development, increased international travel, microbial adaptation and lapses in public health measures. Biomedical research has allowed us to identify and classify previously uncultured pathogens, characterize microbial virulence factors, create new diagnostic tests and develop vaccines. Here, we highlight a few emerging infections and illustrate the role that molecular medicine has played in furthering our understanding of these diseases.

Methylxanthines with adenosine alter TNF alpha-primed PMN activation.

Methylxanthines are best known as phosphodiesterase inhibitors that cause a rise in intracellular cAMP. One would expect the two methylxanthines, caffeine and pentoxifylline, to have similar actions on neutrophils (PMN). However, caffeine stimulated and pentoxifylline inhibited PMN oxidative activity. Micromolar concentrations of pentoxifylline decreased native and recombinant tumor necrosis factor-alpha (TNF alpha)-primed formyl met-leu-phe (fMLP)-stimulated PMN chemiluminescence, superoxide production and myeloperoxidase (MPO) release. In contrast, equal concentrations of caffeine increased chemiluminescence and MPO release with no effect on superoxide production. These activities of the methylxanthines were only observed in the presence of physiological concentrations of adenosine, and were abolished by the treatment of the PMN with adenosine deaminase. The activities of adenosine, pentoxifylline and caffeine on PMN activity could not be readily explained by changes in PMN [cAMP]. Thus for TNF alpha-primed PMN, pentoxifylline decreases PMN activity by enhancing the effect of adenosine on degranulation and superoxide production; whereas caffeine increases PMN activity by counteracting the effect of adenosine on degranulation.

Adenosine modulation of tumor necrosis factor-alpha-induced neutrophil activation.

We hypothesized that adenosine, known to be release from inflammatory sites, could lessen the potentially damaging activity of neutrophils (PMN) primed by tumor necrosis factor-alpha (TNF alpha) at sites of infection. We investigated the effect of adenosine on PMN primed with cell-free medium from mononuclear leukocytes (MNL) that had been treated with lipopolysaccharide (LPS) yielding a conditioned medium rich in TNF alpha and on PMN primed with recombinant human TNF alpha (rhTNF alpha). LPS (10 ng/mL) minimally primed PMN, but LPS-MNL-conditioned medium increased PMN chemiluminescence in response to f-Met-Leu-Phe (fMLP) 1242% compared with unprimed PMN. LPS-MNL-conditioned medium contained adenosine (approximately 30 nM). Converting the adenosine in the LPS-MNL-conditioned medium to inosine with adenosine deaminase (ADA) or blocking adenosine binding to PMN with the adenosine receptor antagonist 1,3-dipropyl-8-(phenyl-p-acrylate)-xanthine (BW A1433U) resulted in a near doubling of chemiluminescence. The LPS-MNL-conditioned medium contained TNF alpha (836 pg/mL; approximately 1 U/mL). Recombinant human TNF alpha (1 U/mL) primed PMN for a 1033% increase in chemiluminescence. Added adenosine decreased rhTNF alpha-primed PMN chemiluminescence (IC50 approximately 100 nM), and adenosine (100 nM) decreased both superoxide and myeloperoxidase release from rhTNF alpha-primed fMLP-stimulated PMN. The activity of adenosine was counteracted by ADA and BW A1433U, and the modulating effect of adenosine was on the primed response rather than on priming per se. Thus, physiological concentrations of adenosine reduce the effects of recombinant human TNF alpha and native human TNF alpha (released from LPS-treated MNL) on PMN activity. Endogenous adenosine may preclude or minimize damage to infected tissue by damping the TNF alpha-primed PMN oxidative response.

The specific type IV phosphodiesterase inhibitor rolipram combined with adenosine reduces tumor necrosis factor-alpha-primed neutrophil oxidative activity.

Monocytes and macrophages produce tumor necrosis factor-alpha (TNF alpha) in response to microbial products including endotoxin. TNF alpha is a potent primer of neutrophil (PMN) oxidative activity. Certain xanthine phosphodiesterase (PDE) inhibitors such as pentoxifylline have been shown to inhibit stimulated oxidative activity in PMN. In the present study, the non-xanthine PDE type IV inhibitor rolipram (4-[3'-cyclopentyloxy-4'-methoxyphenyl]-2-pyrrolidone) alone and in combination with adenosine is examined as a potential modulator of TNF alpha-primed PMN oxidative activity. Attainable in vivo concentrations of rolipram and physiological concentrations of adenosine alone and together synergistically decreased rhTNF alpha-primed suspended PMN oxidative activity stimulated by the chemoattractant f-met-leu-phe. The rolipram effect was reversible by washing, and rolipram had a comparable effect if added before or after priming, indicating that its effect was on the primed response rather than on priming per se. In addition, rolipram especially when combined with adenosine, decreased rhTNF alpha-stimulated PMN adherence to a fibrinogen-coated surface, and the oxidative burst of rhTNF alpha-stimulated adherent PMN. The specific adenosine A2a receptor agonists CGS 21680 and WRC-0474 had comparable activity to adenosine in these experiments. Adenosine (or CGS 21680) combined with rolipram synergistically increased f-met-leu-phe-stimulated PMN cAMP content. The effects of both adenosine and rolipram with adenosine could be only partly counteracted by treatment of the PMN with the protein kinase A inhibitor KT 5720, indicating that protein phosphorylation is only partially involved. Rolipram activity was about 1000 x (by molar concentration) greater than pentoxifylline in comparable assays. Thus, rolipram, especially when combined with adenosine, has potent modulating effects on PMN activation and may be useful in decreasing inflammatory tissue damage in patients with sepsis.

Adjuncts to antibacterial therapy.

Strategies of augmenting or attenuating the immune system's response to infection are promising potential methods to enhance antibacterial therapy. Many of these new therapies are natural cytokines, such as the hematopoietic growth factors and interferons, which upregulate the immune response. Other examples include replacement therapies, such as immune globulin, and downregulators of the immune response, such as corticosteroids. In the near future it may be possible to adjust the host response to microbial infection to maximally inhibit the microbe while minimizing inflammatory damage.