Effects of Preemptive Analgesia on Pain and Cytokine Production in the Postoperative Period

Background: The postoperative period is associated with increased production of proinflammatory cytokines, which are known to augment pain sensitivity, among other effects. In a previous study, the authors found that patients treated with patient-controlled epidural analgesia (PCEA) exhibited attenuated proinflammatory cytokine response in the postoperative period. In the present study, the authors examined whether preemptive analgesia continued with PCEA may further attenuate the proinflammatory cytokine response and reduce pain sensitivity in the postoperative period. They compared cytokine production in two groups of patients, one receiving PCEA, the other receiving preemptive epidural analgesia continued by PCEA.

Methods: Female patients hospitalized for transabdominal hysterectomy were randomly assigned to one of two pain management techniques: PCEA or preemptive epidural analgesia followed by PCEA (PA + PCEA). Postoperative pain was assessed using the visual analog scale. Blood samples were collected before, 24, 48, and 72 h following surgery. Production of the following cytokines was assessed ex vivo in stimulated peripheral blood mononuclear cells: interleukin (IL)-1[beta], tumor necrosis factor [alpha], IL-6, IL-1ra, IL-10, and IL-2.

Results: Patients of the PA + PCEA group exhibited lower pain scores throughout the 72 h postoperatively, compared with patients of the PCEA group. In patients of the PA + PCEA group in the postoperative period, production of IL-1[beta], IL-6, IL-1ra, and IL-10 was significantly less elevated, while IL-2 production was significantly less suppressed.     

HELLP syndrome associated with factor V R506Q mutation

The pathogenesis of HELLP (haemolysis, elevated liver enzyme and low platelet count) syndrome, a severe presentation of pre-eclampsia, is still an enigma. Activated protein C resistance resulting from a mutation in coagulation factor V has recently emerged as the leading cause of thrombosis in pregnancy. We report on two patients with HELLP syndrome who were found to be heterozygous for factor V R506Q mutation, leading to activated protein C resistance. These findings suggest that the pathogenesis of HELLP syndrome is associated with a thrombotic process, and point to the potential benefit of anti-thrombotic therapy in this condition.     

Effects of mono-, di-, and triamines on the N-methyl-D-aspartate receptor complex: a model of the polyamine recognition site.

Systematic series of monoamines, diamines, and triamines were used to define the structural requirements for interaction at the polyamine recognition site of the N-methyl-D-aspartate receptor complex. Effects of amines on binding of [3H]MK-801 to washed synaptic plasma membranes were measured in the presence of L-glutamate and glycine (100 microM each), in the absence or presence of spermine (10 microM). Linear aliphatic monoamines of methylene chain length up to 12 (dodecylamine) did not interact with the polyamine recognition site. Nonspecific inhibition of binding was observed at high concentrations of the longer monoamines. alpha,omega-Diamines of methylene chain length 2 (1,2-diaminoethane, DA2) through 12 (1,12-diaminododecane, DA12) had varying actions, depending on chain length. The shortest diamines (DA2 and DA3) acted as weak partial agonists, enhancing the binding of [3H[MK-801. Intermediate-length diamines (DA4-DA7) were selective polyamine antagonists, having little or no effect on binding of [3H]MK-801 measured in the absence of spermine but inhibiting binding measured in the presence of spermine. The longest diamines tested (DA8-DA12) acted as inverse agonists; they inhibited binding in the absence or presence of spermine, and this inhibition was blocked by the selective polyamine antagonist diethylenetriamine. Computer modeling of conformations of the diamines quantitatively documented that 1) these molecules are flexible and 2) long diamines may easily adopt conformations with inter-nitrogen distances mimicking those of short diamines. The cis and trans isomers of 1,4-diaminocyclohexane are inflexible, conformationally restricted diamines with markedly different actions. The cis isomer was a partial agonist and the trans isomer was an antagonist at the polyamine recognition site. Triamines of general structure NH2(CH2)3NH(CH2)xNH2 (TRI[3,x]), in which x = 3-12, were synthesized and tested for activity at the polyamine recognition site. Despite the large range of size, TRI[3,3] through TRI[3,9] were all fully polyamine agonists of similar potency. TRI[3,10] was a partial agonist, whereas TRI[3,12] inhibited binding of [3H]MK-801. Diethylenetriamine did not attenuate the effect of TRI[3,12]. Based on the results of the radioligand binding studies and the computer analysis, a model of the polyamine recognition site is proposed.     

Human studies concerning thermal-induced shivering, postoperative "shivering," and cold-induced vasodilation

Human reaction to cold stress and hypothermia involves shivering. Another form of overt shaking, postoperative shivering, has been attributed as a thermoregulatory response to postoperative hypothermia. Analysis of the normal human shivering pattern showed a synchronized, slow amplitude modulation (six to eight cycles/min) over all muscles sampled. In addition, there was a frequency of 8 to 10 Hz associated with each low-frequency amplitude modulation. EMG signals from postoperative patients revealed none of the major patterns seen in thermal-induced shivering. Cold-induced vasodilation also was studied and found to occur simultaneously in all cold-stressed fingers regardless of size or innervation. Thermal shivering and cold-induced vasodilation are considered to be manifestations of central neural oscillators.     

Radionuclide venography vs Tc-99m-RBC equilibrium angiography: A comparative paired study

Combined direct injection venography (DIV) and equilibrium angiography (EA) were performed in 13 patients, by injecting in vitro labeled ^99mTc autologous RBC, via pedal veins, and imaging the first pass and the equilibrium phase. This paired comparative study of DIV with EA shows that DIV has advantages over EA because it provides selective information on the deep venous system from the calves to the inferior vena cava. DIV provides information on the flow dynamics and the high contrast first pass images provide better definition of non filling venous segments as well as visualization of collaterals. When using ^99mTc-MAA, lung perfusion can also be imaged. DIV is recommended as the procedure of choice for the diagnosis of DVT and EA should be employed only when pedal vein injection is not possible.     

Inhibition and superactivation of the calcium-stimulated isoforms of adenylyl cyclase

It was shown previously that chronic exposure to opiate agonists increases adenylyl cyclase (AC) activity, a phenomenon termed AC superactivation (or supersensitization). More recently, we showed that acute G_i/o-coupled receptor activation inhibits the activity of several AC isozymes, including Ca²⁺/calmodulin-stimulated AC-I and -VIII, whereas chronic receptor activation induces their superactivation. Here, we report that both acute μ-opioid receptor-induced inhibition and chronic induced superactivation of AC-I and -VIII are pertussis toxin sensitive. In addition, we show that proteins that interfere with the activity of {ie195-2} subunits ({ie195-3} scavengers) strongly attenuate the acute inhibition of AC-I and -VIII and the superactivation of AC-I, and abolish the superactivation of AC-VIII. Based on these results, we suggest that {ie195-4} is involved in the acute inhibition and chronic agonist-induced superactivation of AC types I and VIII.     

Good outcome in prune-belly syndrome despite associated severe anomalies

A boy aged 4.5 years with prune-belly syndrome (PBS) and associated urethral stenosis, oligohydramnios, imperforate anus and vesicosigmoid fustula is described. In contrast to the anticipated poor prognosis, vesicostomy and divided transverse colostomy performed after birth followed by prophylaxis of infection and bicarbonate supplementation have resulted in a good outcome. The vesicosigmoid fistula might have served in utero as a natural diversion protecting from pressure-induced renal damage. It is suggested that the main determinant of prognosis in PBS is the presence and degree of kidney dysplasia at birth as reflected by the neonatal renal function after performance of an indicated urinary diversion procedure rather than the presence of severe associated anomalies.Supported in part by grants from the National Institute of Health AM 37223-01 and the Medical School and Graduate School Research Committees of the University of Wisconsin and a Research Career Development Award KO4 AM 00421 (RWC), by the Pearl M. Stetler Foundation (SD) and by a National Kidney Foundation fellowship (IZ)     

Investigation of an outbreak of Salmonella enteritidis gastroenteritis associated with consumption of eggs in a restaurant chain in Maryland

Salmonella enteritidis ser. enteritidis was isolated from patrons and employees of three restaurants in a restaurant chain in Maryland during August and September 1985. Isolates from all three restaurants had identical plasmid profiles; this profile was present in 13 of 40 randomly selected S. enteritidis isolates received by the Maryland state health department laboratory during a comparable time period. The outbreak in one restaurant resulted in at least 71 illnesses, with 17 persons known to have been hospitalized. Scrambled eggs served on a "breakfast bar" were implicated as the vehicle of transmission in this restaurant, with eggs a possible vehicle in another of the three restaurants. The data point out the risks associated with improper handling of eggs in food service establishments, provide further evidence for the observed association between S. enteritidis and eggs in the northeastern United States, and demonstrate the utility of plasmid analysis in investigation of outbreaks involving common Salmonella serotypes.     

Effectiveness of neonatal transport in New York city in neonates less than 2500 grams—A population study

In the past two decades, there has been a gradual trend to regionalization of perinatal care, categorization of hospitals and transport services for neonatal health care. The literature alludes to both beneficial and deleterious effects of neonatal transport (T) but no controls such as a matched nontransport (NT) population have been utilized to date.The major goal of this study was to evaluate the effect of neonatal transport from Level I and II high risk 2500 gm. neonates (born in NYC in one calendar year, 1979) compared to a cohort nontransported population matched for hospital of birth, weight, race, sex and risk. All transported 2500 gm. from Level I and II (n=328) were studied and a stratified random sample of the nontransported (NT) infants 2500 gm. from these same hospitals (n=2042) was used for comparison. The principle outcome variable was survival. The major conclusion of this study is that in Level I and II hospitals the transport group had a significantly increased survival in infants who were sick (Apgar <6) compared to cohorted nontransported controls. Interhospital differences in survival were noted among Level I and II but not seen in the subdivisions of (A) and (B) hospitals.Angelo Ferrara, M.D., Ph.D., is Professor, Pediatrics, NYU Medical Center, New York, N.Y.: Melvin Schwartz, M.D., was Research Professor, Environmental Medicine, NYU Medical Center, New York, N.Y.; Helen Page, R.N., M.P.A., is Quality Assurance Reviewer, Manhattan Eye, Ear, Throat Hospital, New York, N.Y.: Morton Israel, M.A., is Research Scientist, Health Resources Administration, City of N. Y., New York, N.Y.; Yucel Atakent, M.D., M.S., is Clinical Associate Professor, NYU Medical Center, New York, N.Y.; C.E. Smith, Ph.D., is President, Health Policy Analysis & Accountability Network, Inc. (HPAAN), Edgewood, New Mexico; Leon Landovitz, Ph.D., is Vice President, Management Information Systems, Healthways System Inc., Islin, N.J.Supported by NCHSR Grant #5-R018-HSO3832