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Biomedical subjects

G Mandell

Publications and source records attributed to G Mandell.

At least 19 recordsLinked to original sources

Local anesthetics attenuate lysophosphatidic acid-induced priming in human neutrophils.

UNLABELLED: Lysophosphatidic acid (LPA) is an intercellular phospholipid mediator with a variety of actions that suggest a role in stimulating inflammatory responses. We therefore studied its actions on neutrophil (PMN) motility and respiratory burst. Because local anesthetics (LA) inhibit LPA signaling and attenuate PMN responses, we also investigated the effects of LA on these actions. Chemotaxis of human PMNs under agarose toward LPA (10(-10)-10(-3) M) was studied, with and without 1 h prior incubation in lidocaine (10(-9)-10(-4) M). Priming as well as activating effects of LPA on PMNs were measured using a cytochrome-c assay of superoxide anion (O2-) production. PMNs were incubated with lidocaine, tetracaine, or S-(-) ropivacaine (all at 10(-6)-10(-4) M) for 10 min or 1 h to assess interference with LPA signaling. LPA demonstrated chemoattractive effects towards human PMNs; this effect was concentration-dependently attenuated by lidocaine. LPA alone did not activate PMNs. However, it acted as a priming agent. LA in clinically relevant concentrations decreased (O2-) production induced by LPA/N-formylmethionine-leucyl-phenylanaline. LPA acts as a chemoattractant and priming agent; however, it does not activate PMNs. LA, in clinically relevant concentrations, attenuate chemotactic and metabolic responses as a result of LPA. These results may explain the antiinflammatory effect of local anesthestics. IMPLICATIONS: Lysophosphatidic acid (LPA) influences two functions of human neutrophils, migration and metabolic activity. It acted as a chemoattractant and a priming-but not activating-agent. Responses to LPA were attenuated by local anesthetics in clinically relevant concentrations.

Anesthetics, Local↗

Epidural labor analgesia and neonatal sepsis evaluation rate: a quality improvement study.

UNLABELLED: Labor epidural analgesia (LEA) is allegedly associated with maternal fever and an increase in the newborn sepsis work-up (SWU) rate. In this study, we evaluated whether LEA causes an increase in the SWU rate compared with a Control group given parenteral narcotics for labor pain. Maternal and neonatal data were collected prospectively for a continuous quality improvement database. Odds ratios were calculated by using multiple logistic regression for various triggers for SWU in the neonate. Of the 1177 primiparous women and their neonates studied, 922 women received LEA and 255 women received parenteral analgesics. A small but statistically significant increase in maternal and neonatal temperatures occurred in parturients receiving LEA. The SWU rates were 7.5% in the LEA group and 9.4% in the Controls (not significant). Triggers identified for SWU were birth weight (odds ratio = 116, P = 0.000), gestational age (odds ratio = 86.6, P = 0.000), meconium aspiration and respiratory distress requiring intubation (odds ratio = 8.6, P = 0.000), hypothermia at birth (odds ratio = 7.1, P = 0.001), maternal Group B beta-hemolytic streptococcal colonization (odds ratio = 6, P = 0.000), and preeclampsia or hypertension (odds ratio = 3.5, P = 0.03). There was no association between LEA and SWU. IMPLICATIONS: Although it has been suggested that epidural analgesia for labor contributes to an increase in neonatal sepsis work-up (SWU), this retrospective analysis shows that epidural analgesia is not associated with an increase in SWU. The factors that were found to contribute to SWU included low birth weight, low gestational age, meconium aspiration or respiratory distress at birth, hypothermia at birth, maternal group B beta-hemolytic colonization, and preeclampsia or hypertension.

Adult↗

Influence of fluconazole at subinhibitory concentrations on cell surface hydrophobicity and phagocytosis of Candida albicans.

Cell surface hydrophobicity (CSH) status influences virulence of Candida albicans and decreases the susceptibility of yeast cells to phagocytic killing. We tested whether subinhibitory concentrations of fluconazole, which is widely used in the treatment and prophylaxis of candidiasis, affect CSH and the susceptibility of C. albicans to enzymatic digestion by glucanase and to phagocytic killing. Treatment of yeast cells with subinhibitory fluconazole concentrations resulted in greater phagocytosis. This effect was independent of CSH but may be related to increased cell wall porosity resulting from alterations in the cell envelope. The use of subinhibitory concentrations of fluconazole in patients with competent phagocytes may contribute to resistance to candidiasis regardless of yeast CSH status.

Antifungal Agents↗

Comparison of ropivacaine 0.1%-fentanyl and bupivacaine 0.125%-- fentanyl infusions for epidural labour analgesia.

PURPOSE: To compare analgesic efficacies of ropivacaine-fentanyl and bupivacaine-fentanyl infusions for labour epidural analgesia. METHODS: In this double- blind, randomized study 100, term, nulliparous women were enrolled. Lumbar epidural analgesia (LEA) was started at cervical dilatation < 5 cm using either bupivacaine 0.25% followed by bupivacaine 0.125% + 2 microg x ml(-1) fentanyl infusion (n=50) or ropivacaine 0.2% followed by ropivacaine 0.1% + 2 microg x ml(-1) fentanyl infusion (n=50). Every hour maternal vital signs, visual analog scale (VAS) pain score, sensory levels, and motor block (Bromage score) were assessed. Data were expressed as mean +/-1 SD and analyzed using Chi -Squared and Mann-Whitney U tests at <0.05. RESULTS: The onset times were 10.62+/-4.9 and 11.3+/-4.7 min for the bupivacaine and ropivacaine groups respectively (P = NS). The median VAS scores were not different between the groups at any of the evaluation periods. However, at least 80% of patients in the ropivacaine group had no demonstrable motor block after the first hour compared with only 55% of patients given bupivacaine (P =0.01). CONCLUSIONS: Both bupivacaine and ropivacaine produce satisfactory labour analgesia. However, ropivacaine infusion is associated with less motor block throughout the first stage of labour and at 10 cm dilatation.

Adult↗

Maternal and fetal effects of labetalol in pregnant ewes.

Labetalol has been advocated to rapidly decrease blood pressure in preeclamptic women and to blunt the hemodynamic response to tracheal intubation. To assess labetalol's actions in a setting of uterine vasoconstriction, saline or labetalol (1 mg/kg) was infused into maternal venous catheters in 12 pregnant ewes receiving continuous maternal intravenous infusions of norepinephrine. Norepinephrine increased maternal mean arterial pressure (MAP) to 120 +/- 4% of control and decreased uterine blood flow to 45 +/- 6% of control. Labetalol, but not saline, altered these parameters: it decreased MAP to 101 +/- 3% and increased uterine blood flow to 70 +/- 7% of prenorepinephrine values. In the second protocol, to assess the degree of labetalol-induced fetal adrenergic blockade, 7 pregnant ewes received, on separate days, saline or labetalol (0.3, 1.0, 3.0 mg/kg) via a maternal venous catheter. Maternally administered labetalol produced minor (less than 12%) decreases in maternal and fetal MAP, without significantly altering heart rate (HR). At each labetalol dose, the degree of alpha- and beta-adrenergic blockade, determined by phenylephrine and isoproterenol challenge, was greater in the ewe than in the fetus. In the near-term pregnant ewe, intravenous (iv) bolus administration of labetalol ameliorated the effects of increased circulating norepinephrine on maternal MAP, uterine blood flow, and fetal pH and arterial O2 tension (PaO2), and produced less adrenergic blockade in the fetus than in the mother.

Adrenergic alpha-Antagonists↗

New pharmacological studies with pentoxifylline.

Polymorphonuclear (PMN) overactivation plays a critical role in microcirculation as well as in conditions such as multiorgan failure (MOF). Pentoxifylline has been shown to prevent PMN activation by endotoxin and cytokines such as TNF alpha and IL-1. In addition, MOF induced by IL-2 in animals can be prevented by pentoxifylline. The present studies evaluated two aspects of PMN activation and pentoxifylline interaction. The first was the time sequence for pentoxifylline prevention of TNF alpha activation and the second was the activity of pentoxifylline on amphotericin B activation of PMNs. TNF alpha activation of PMNs is blocked by pentoxifylline when cells are exposed to pentoxifylline prior to TNF alpha or after TNF alpha. Amphotericin B activation of PMNs was demonstrated by a decreased chemotaxis, increased chemiluminescence, and increased PMN spreading. In all conditions, pentoxifylline decreased amphotericin B activation of PMNs. These results suggest that pentoxifylline can reverse cytokine activation of PMNs and that pentoxifylline may alter some of the toxic effects of amphotericin.

Amphotericin B↗

Prolonged left ventricular dysfunction induced by sequential multifocal ischemic infarcts in dogs.

A method of creating multifocal ischemia in animals leading to left ventricular (LV) functional impairment is described. In a series of 10 mongrel dogs, electrodes were implanted in multiple branches of the coronary arteries. Subsequently, in seven animals, an 800-microA anodal current was applied for 3 h repeatedly over a span of 4-9 weeks. After current application, serum creatine kinase cardiac isoenzyme increased by 12.2 +/- 4.6 U/L (p less than 0.01) and ischemic electrocardiographic changes were consistently present. After an average of 10.7 current applications, all animals were tachypneic on mild exertion. Repeated measurement of LV function demonstrated a substantial reduction in cardiac reserve. No significant changes in three control animals were observed. The animals were sacrificed 80 days (range 49-108 days) after the initial current application. Presacrifice cineangiography and postmortem examination disclosed coronary artery occlusions, stenoses, recanalizations, and collateralization in the distributions expected on the basis of the time elapsed since electrode activation. In all cases, the myocardium exhibited diffuse fibrosis. This method reliably brings about multifocal myocardial ischemic changes in dogs and may provide a chronic LV failure model particularly suitable for the evaluation of LV assist systems.

Animals↗

Unusual appearance of a highly vascular lesion on Tc-99m DISIDA hepatobiliary scintigraphy.

A lesion was identified on the late images of a hepatobiliary scintigraphic study, but was not detected on the very early images, due to its enlarged blood pool. This combination of scan findings has not been previously described. The implication of the observation is that one must examine all the images of the hepatobiliary study in an effort to detect space-occupying lesions of the liver.

Aged↗

Carbon dioxide laser surgery of the eye and adnexa.

A carbon dioxide laser which functions in both rapid superpulsed and continuous wave mode for use in ophthalmic surgery is described. Rapid superpulsed mode was found more effective in the creation of trabeculectomy-like procedures in glaucomatous human eyes with satisfactory results in 12 of 14 eyes treated. Continuous wave energy was found to be superior when full thickness eye wall resection was performed. The carbon dioxide laser was found to be effective in hemostatic resection and ablation of skin lesions about the eye. Rapid superpulse was found to be more effective when puckering and tissue loss were to be minimized, while continuous wave was found to be effective when shrinkage of tissue, as in the performance of a Ziegler cautery type repair for ectropion, was preferred. Rapid superpulse was found to be more controllable in experimental phacovaporization in cats with anterior capsulotomy being easily performed. Continuous wave was found to be a more efficacious modality for corneal shrinkage although attempts at present to create permanent corneal alterations have been fruitless.

Animals↗

An extravascular left ventricular assist device.

The hemodynamic efficacy and prosthesis-vessel interaction of a pneumatically activated circulatory assist device was investigated in 12 acute and 12 chronic studies in dogs. A polyurethane balloon encased in Dacron-velour cloth was fastened to the descending thoracic aorta with a spiral wrapping of Dacron graft material. Diastolic augmentation was provided by rhythmic inflation and deflation of the balloon. Hemodynamic results, based on 5 dogs with experimental myocardial ischemia, showed that left ventricular systolic peak pressure decreased by 8.2 +/- 1.9%, cardiac output increased by 13.1 +/- 2.8%, and circumflex coronary artery flow rose by 17.5 +/- 2.5%. In the chronic experiments the prosthesis was asynchronously but continuously activated from one to sixteen weeks at 74 cycles per minute. Postmortem examination of the implantation site in all 12 dogs showed that necrosis had developed but was limited to the outer half of the medial layer beneath the pumping chamber and that the aortic wall was compressed to about 70% of its original thickness. Although the method described represents a simple form of providing ventricular assistance, its applicability for long-term circulatory support remains to be evaluated.

Animals↗

Permanent in-series cardiac assistance with the dynamic aortic patch: Blood-prosthesis interaction in long-term canine experiments.

The blood-prosthesis interaction of the dynamic aortic patch (DAP), an in-series assist device for permanent circulatory support which is implanted in the descending thoracic aorta, was studied in 65 long-term experiments. Periods of postoperative observation with the device inactive or activated ranged from 2 weeks to 22 months. The intravascular surface of the DAP, fabricated of Dacron velour backed by bioelectric polyurethane, displayed various degrees of organization, ranging from a thin fibrin layer to a well organized pseudointima. Activation of the system did not prevent the development of an organized pseudointima. Changes in free-plasma hemoglobin were minimal; platelet count per square millimeter and state of reactivity remained within normal limits. Evidence of renal embolization, attributable to activation of the device, was found in five animals. Frequent lethal complications were aortic rupture and infections of the thoracic cavity originating at the implantation site. Further improvement of the DAP and the techniques of implantation is indicated to insure its efficacy during long-term implantation and activation.

Animals↗