Warfarin therapy and perioperative transfusion requirement with bleeding amount in patients undergoing cardiac surgery with cardiopulmonary bypass: a retrospective study.

OBJECTIVES: The study was designed to evaluate the effect of warfarin on perioperative transfusion, bleeding and coagulation status in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). BACKGROUND: There were controversy about the effect of warfarin on perioperative transfusion and bleeding. METHODS/MATERIALS: Medical records from 107 consecutive patients with atrial fibrillation (AF) on warfarin therapy undergoing cardiac surgery with cardiopulmonary bypass (CPB) from 2008 to 2013 at a single university teaching hospital were retrospectively reviewed to compare the patients on to those not on warfarin therapy in terms of perioperative transfusion requirement, postoperative 24-h bleeding amount, and coagulation status assessment using prothrombin time (PT), international normalised ratio (INR) and rotational thromboelastometry (ROTEM®). RESULTS: Although PT/INR was significantly prolonged both before and after surgery in patients on warfarin therapy, ROTEM® data, perioperative transfusion requirement and postoperative 24-h bleeding amount (785 ± 331 vs 676 ± 303 mL, P = 0·089, respectively) were not significantly different between the patients on and those not on warfarin therapy. CONCLUSION: In patients on warfarin therapy undergoing cardiac surgery with CPB, warfarin therapy did not significantly increase perioperative transfusion requirement and bleeding.

Eop1 from a Rubus strain of Erwinia amylovora functions as a host-range limiting factor.

Strains of Erwinia amylovora, the bacterium causing the disease fire blight of rosaceous plants, are separated into two groups based on host range: Spiraeoideae and Rubus strains. Spiraeoideae strains have wide host ranges, infecting plants in many rosaceous genera, including apple and pear. In the field, Rubus strains infect the genus Rubus exclusively, which includes raspberry and blackberry. Based on comparisons of limited sequence data from a Rubus and a Spiraeoideae strain, the gene eop1 was identified as unusually divergent, and it was selected as a possible host specificity factor. To test this, eop1 genes from a Rubus strain and a Spiraeoideae strain were cloned and mutated. Expression of the Rubus-strain eop1 reduced the virulence of E. amylovora in immature pear fruit and in apple shoots. Sequencing the orfA-eop1 regions of several strains of E. amylovora confirmed that forms of eop1 are conserved among strains with similar host ranges. This work provides evidence that eop1 from a Rubus-specific strain can function as a determinant of host specificity in E. amylovora.

Tsc13p is required for fatty acid elongation and localizes to a novel structure at the nuclear-vacuolar interface in Saccharomyces cerevisiae.

The TSC13/YDL015c gene was identified in a screen for suppressors of the calcium sensitivity of csg2Delta mutants that are defective in sphingolipid synthesis. The fatty acid moiety of sphingolipids in Saccharomyces cerevisiae is a very long chain fatty acid (VLCFA) that is synthesized by a microsomal enzyme system that lengthens the palmitate produced by cytosolic fatty acid synthase by two carbon units in each cycle of elongation. The TSC13 gene encodes a protein required for elongation, possibly the enoyl reductase that catalyzes the last step in each cycle of elongation. The tsc13 mutant accumulates high levels of long-chain bases as well as ceramides that harbor fatty acids with chain lengths shorter than 26 carbons. These phenotypes are exacerbated by the deletion of either the ELO2 or ELO3 gene, both of which have previously been shown to be required for VLCFA synthesis. Compromising the synthesis of malonyl coenzyme A (malonyl-CoA) by inactivating acetyl-CoA carboxylase in a tsc13 mutant is lethal, further supporting a role of Tsc13p in VLCFA synthesis. Tsc13p coimmunoprecipitates with Elo2p and Elo3p, suggesting that the elongating proteins are organized in a complex. Tsc13p localizes to the endoplasmic reticulum and is highly enriched in a novel structure marking nuclear-vacuolar junctions.

A Case of Ectopic Paragonimiasis in a 17th Century Korean Mummy.

Archaeoparasitological studies on fossilized feces obtained from Joseon Dynasty (1392-1910 CE) mummies have provided invaluable data on the patterns of parasitic infection in pre-modern Korean societies. In our recent radiological investigation of a 17th century Joseon mummy discovered in Cheongdo (South Korea), we located a liver mass just below the diaphragm. Anatomical dissection confirmed the presence of a mass of unknown etiology. A subsequent parasitological examination of a sample of the mass revealed a large number of ancient Paragonimus sp. eggs, making the current report the first archaeoparasitological case of liver abscess caused by ectopic paragonimiasis.

Melatonin Its intracellular and genomic actions.

Besides its actions via membrane receptors on cells in specific areas of the brain and peripheral tissues, melatonin also has direct intracellular actions. The neurohormone melatonin is a potent free radical scavenger in vitro and a powerful antioxidant in vivo. Studies to date indicate that it is a better scavenger of the highly toxic hydroxyl and peroxyl radicals than some other known compounds. Melatonin also prevents the toxicity of singlet oxygen and stimulates the antioxidative enzyme, glutathione peroxidase. Considering its varied and potent antioxidant capability, it is possible that melatonin is an essential element of the antioxidant defense system of organisms. Besides these direct intracellular actions of melatonin, it was recently discovered that the indole also has binding sites in the nucleus of many cells. Melatonin's genomic actions are believed to follow its binding to these nuclear loci.

Melatonin prevents changes in microsomal membrane fluidity during induced lipid peroxidation.

We tested the effect of melatonin on membrane fluidity in microsomes of a rat liver model in which lipid peroxidation was induced by the addition of FeCl3, ADP and NADPH. Membrane fluidity was monitored using fluorescence spectroscopy and lipid peroxidation was estimated by quantifying malonaldehyde (MDA)+4-hydroxyalkenals (4-HDA) concentrations following the induction of lipid peroxidation with and without pre-incubation with melatonin (1 microM-3 mM). Membrane rigidity increased during induced lipid peroxidation while melatonin reduced in a concentration-dependent manner both membrane rigidity and MDA+4-HDA generation. Melatonin's protective effect may relate to its known ability to scavenge free radicals and function as an antioxidant.

Delayed response to orthoclone OKT3 treatment for renal allograft rejection resistant to steroid and antilymphocyte globulin.

Since February 1986, 23 patients have received Orthoclone OKT3 treatment at our transplant center for renal allograft rejection resistant to steroids and antilymphocyte globulin (ALG). They have been followed for at least 4 months as of this study time (range: 4-15 months). We report here our experience with OKT3, including five late responders--as late as 116 days after OKT3 treatment. Overall rejection was reversed in 19/23 (83%). Rejection was controlled in 95% of primary and 50% of nonprimary transplants; 89% of the male and 80% of the female patients were treated successfully; 94% of the cadaver-donor and 80% of the living-donor transplants responded successfully. The one-year rerejection rate after OKT3 was 50%, and 38% of rerejection episodes were treated successfully. Time (days) required to reverse the episodes of acute graft rejection after the start of OKT3 is plotted, and it shows a distinctive bimodal distribution: first, early responders with a mean +/- SD of 12 +/- 5 days (range: 4-20 days) and second, late responders with a mean +/- SD of 58 +/- 31 days (range: 30-116 days). We conclude that OKT3 is very effective in treating steroid- and ALG-resistant acute rejection episodes, and also that it is important to be aware of the potential late response to OKT3 antirejection therapy and recommend delaying transplant nephrectomy or immunosuppressive withdrawal for as long as possible (probably up to 4 months) for patients who have received OKT3 treatment.

Withdrawal of steroid immunosuppression in renal transplant recipients.

The complications of long-term steroid immunosuppression are well known. During a 12-month period, 52 living-donor renal transplant recipients were entered into a protocol of intentional early steroid withdrawal. Selection criteria were primary living-related renal transplants in HLA-identical (12) or one-haplotype match (40) patients. The study population consisted of 25 diabetics (48.1%) with a mean age of 32.4 years. All patients received preoperative blood transfusions (3 donor-specific in haplotype-matched, 3 random in HLA-identical recipients). Immunosuppression consisted of cyclosporine, azathioprine, and corticosteroids, with deliberate steroid withdrawal after two weeks. Forty-six patients (88.5%) were successfully tapered off steroids, while the six protocol failures (11.5%) were due to early rejection or leukopenia that prevented steroid withdrawal. Twenty-three patients (50%) subsequently were returned to steroid therapy for rejection (21) or leukopenia (2). Inadequate immunosuppression precipitated six rejection episodes and were preventable, while the remaining 15 were true breakthrough crises. The overall rejection rate was 50%, with 92.3% of initial rejection episodes occurring within five weeks of steroid withdrawal. Rejection episodes were responsive to steroid therapy alone in 73.2% of cases. No graft loss from rejection has occurred after a mean follow-up interval of 8.5 months. At present, 33 patients (63.5%) are off steroids. In HLA-identical recipients, all but one successfully completed the protocol and 75% are currently steroid-free. In haplotype-matched patients, 87.5% completed the protocol and 60% are steroid-independent. Comparison with well-matched control groups on steroids failed to reveal any difference in graft or patient survival, rejection, infection, or mean serum creatinine level. No discriminating risk factors could be identified that were predictive of steroid withdrawal success or failure. In select patients, early steroid withdrawal can be accomplished without jeopardizing graft function. Long-term follow-up is required to assess the risk-benefit ratio of steroid withdrawal upon immunosuppressive morbidity.

Kidney retransplantation in the cyclosporine era.

The results of kidney retransplantation in the cyclosporine era remain to be determined. Over a 42-month period, 76 nonprimary renal transplants (66 second, 7 third, 3 fourth allografts) were performed in 73 recipients under cyclosporine immunosuppression. The patient population was predominantly white (90.4%) with a mean age of 32.3 years. Twenty-one recipients (28.8%) were diabetic, and 36 (49.3%) were highly sensitized (panel-reactive antibody [PRA] greater than 50%). Sixty-two patients received cadaver donor grafts while the remaining donations were living-related (12) or living-unrelated (2). A sequential antilymphocyte globulin/cyclosporine protocol was employed, with cyclosporine therapy delayed until adequate renal function occurred. Overall patient and graft survival is 92.1% and 60.5%, respectively, after a mean follow-up of 20.0 months. The mean serum creatinine is 1.64 mg/dl in the 46 functioning allografts. Graft survival is 63.6% for secondary grafts, 28.6% for tertiary grafts, and 66.7% for fourth kidney transplants. In second transplants, recipients of cadaver donor kidneys have a graft survival of 58.5%, while living-related donor graft survival is 84.6% (P = 0.07). In the cadaver retransplant population, duration of previous transplant function greater than one year and HLA-DR matching were associated with increased graft survival, while age over 39 and presence of diabetes mellitus with reduced graft survival. However, these trends were not significant. Peak PRA above 50% did demonstrate a significant negative impact on graft survival both in the univariate and multivariate analyses of risk factors. Acute rejection occurred in 50 patients (65.8%), and was successfully reversed 50% of the time. Of the 30 grafts lost, 25 (83.3%) occurred within four months of retransplantation. Transplant nephrectomy was performed in 20 patients. Cyclosporine was not administered in 21 (70%) of these early graft failures, negating any potential beneficial effect. Retransplantation can be performed safely, with living-donor graft survival superior to cadaver retransplant rates. Rejection and early graft loss are common, especially in the highly sensitized patient. The impact of cyclosporine immunosuppression in renal retransplantation is much less dramatic than in primary transplantation in a protocol that delays cyclosporine therapy until allograft function is demonstrated.

Increased infections associated with the use of OKT3 for treatment of steroid-resistant rejection in renal transplantation.

We compared the infections encountered in 23 renal transplant patients given the monoclonal anti-T-cell antibody, Orthoclone OKT3 (OKT3), for treatment of steroid-resistant rejection in 1986 and in 23 control patients from 1984 to 1985 with resistant rejection matched demographically, for severity of rejection and for risk factors predisposing to infection, who did not receive OKT3; recipients of OKT3 received substantially less prednisone, cyclosporine, and antilymphocyte globulin (ALG) than control patients for treatment of the rejection episode. Fourteen (61%) patients given OKT3 developed one or more infections in the 3-month period following treatment as compared with 9 control patients (39%) given conventional antirejection therapy with high-dose steroids and, usually, ALG. Patients given OKT3 were significantly more likely to develop serious infections (pneumonia, bacteremia, meningitis, or severe viral infection; 16 episodes vs. 4, P = .02). Six recipients of OKT3 (26%) acquired infections typically encountered in states associated with depressed cell-mediated immunity (CMI)--Listeria sepsis (2), disseminated nocardiosis and Mycobacterium tuberculosis infection (1), cytomegalovirus (CMV) pneumonia (1), Yersinia infection with severe dermatophytosis (1), and Epstein-Barr virus-associated lymphoproliferative syndrome (1)--as compared with 1 case of mild CMV infection in the control group (P = .08). Trimethoprim-sulfamethoxazole (TMP-SMZ) was given to 19 patients in each group; all 4 recipients of OKT3 who did not receive TMP-SMZ prophylaxis developed life-threatening infection, 3, bacteremia (2 with Listeria) and 1, disseminated nocardiosis and M tuberculosis infection. These data suggest that OKT3 given for treatment of resistant rejection in renal transplantation predisposes the patient to serious infection, particularly with opportunistic pathogens characteristically associated with depressed cell-mediated immunity. Prophylaxis with TMP-SMZ, which is safe, well tolerated, and effective for reducing the incidence of infection in renal transplantation, may be especially important during OKT3 therapy.

Inhibition by fluoxetine of voltage-activated ion channels in rat PC12 cells.

The effects of fluoxetine (Prozac) on voltage-activated K+, Ca2+ and Na+ channels were examined using the whole-cell configuration of the patch clamp technique in rat pheochromocytoma (PC12) cells. When applied to the external bath solution, fluoxetine (1, 10, 100 microM) decreased the peak amplitude of K+ currents. The K+ current inhibition by fluoxetine (10 microM) was voltage-independent and the fraction of current inhibition was 39.7-51.3% at all voltages tested (0 to +50 mV). Neither the activation and inactivation curves nor the reversal potential for K+ currents was significantly changed by fluoxetine. The inhibition by fluoxetine of K+ currents was use- and concentration-dependent with an IC50 of 16.0 microM. The inhibition was partially reversible upon washout of fluoxetine. The action of fluoxetine was independent of the protein kinases, because the protein kinase C or A inhibitors (H-7, staurosporine, Rp-cAMPS) did not prevent the inhibition by fluoxetine. Intracellular infusion with GDPbetaS or pretreatment with pertussis toxin did not block the inhibitory effects of fluoxetine. The inhibitory action of fluoxetine was not specific to K+ currents because it also inhibited both Ca2+ (IC50 = 13.4 microM) and Na+ (IC50 = 25.6 microM) currents in a concentration-dependent manner. Our data indicate that when applied to the external side of cells, fluoxetine inhibited voltage-activated K+, Ca2+ and Na+ currents in PC12 cells and its action on K+ currents does not appear to be mediated through protein kinases or G proteins.

Modular fluorescence sensors for saccharides.

Modular and modular polymer supported fluorescence photoinduced electron transfer (PET) sensors 2 and 3 with two boronic acid receptor units, a pyren-1-yl fluorophore, and hexamethylene linker show selective saccharide binding in aqueous methanolic solution at pH 8.21.

Melatonin and vitamin E limit nitric oxide-induced lipid peroxidation in rat brain homogenates.

We have investigated the level of lipid peroxidation (LPO) in rat brain homogenates in the presence of nitric oxide (NO) which was released by the addition of sodium nitroprusside (SNP) and compared it with that induced by H2O2. We also examined the effect of melatonin and vitamin E on the NO-induced LPO. The concentration of malonaldehyde (MDA) plus 4-hydroxyalkenals (4-HDA) was used as an index of LPO. While both H2O2 and SNP increased MDA + 4-HDA production in brain homogenates in a concentration-dependent manner, SNP was more potent than H2O2 at all concentrations tested. Both melatonin or vitamin E reduced NO-induced LPO in a dose-dependent manner in concentrations ranging from 10 microM to 10 mM. Under the in vitro conditions of this experiment, vitamin E was more efficient than melatonin in limiting NO-induced LPO in rat brain homogenates.

Characteristics of particle-loaded monolithic sol-gel columns for capillary electrochromatography. I. Structural, electrical and band-broadening properties.

Particle-loaded (3 microm, C18) monolithic sol-gel columns have been prepared and selected characteristics measured. They have a surprisingly high permeability, allowing their operation in the microLC mode at pressures as low as 69 kPa where their efficiency is about 50000 plates per meter and the CEC mode where efficiency is at least 106000 plates per meter. These columns can withstand over 13.8 MPa pressure without compression or movement within the 75 microm capillary. Field strengths in the packed segments are approximately 50% greater than those in the open segments, due to the higher resistivity of the particle-laden regions. There is a relatively rapid loss of efficiency with increasing linear velocity in both the CEC and microLC modes, which may be due to a tortuosity effect in the inter- and intra-particulate voids. Chromatographic behavior is characteristic of conventional C18 particles, indicating that analytes have significant access to the surface within the pores of the immobilized bonded phase.

Genotoxicity of paraquat: micronuclei induced in bone marrow and peripheral blood are inhibited by melatonin.

The ability of melatonin to influence paraquat-induced genotoxicity was tested using micronucleated polychromatic erythrocytes as an index of damage in both bone marrow and peripheral blood cells of mice. Melatonin (10 mg/kg) or an equal volume of saline were administered intraperitoneally (ip) to mice 30 min prior to an ip injection of paraquat (20 mg/kgx2), and thereafter at 6-h intervals until the conclusion of the study (72 h). The number of the micronucleated polychromatic erythrocytes increased after paraquat administration both in peripheral blood and bone marrow cells. Melatonin administration to paraquat-treated mice significantly reduced micronuclei formation in both peripheral blood and bone marrow cells; these differences were apparent at 24, 48 and 72 h after paraquat administration. The induction of micronuclei was time-dependent with peak values occurring at 24 and 48 h. The reduction in paraquat-related genotoxicity by melatonin is likely due in part to the antioxidant activity of the indole. We did not observe effects of melatonin over paraquat in paraquat+melatonin groups incubated at 0, 60 and 120 min. Mitomycin C, which was used as a positive control, also caused the expected large rises in micronuclei in both bone marrow and peripheral blood cells at 24, 48 and 72 h after its administration.

Arterial supply of the nasal tip in Asians.

OBJECTIVES: The blood supply to the nasal tip and columella was examined to determine whether it could be damaged as a result of transcolumellar incision during an external rhinoplasty approach in Asians. METHODS: The blood vessels that supply the nasal tip were examined by dissecting 51 cadavers, and their corresponding 102 nasal sections were injected with red latex before dissection. The size and distribution of the vessels were measured with the unaided eye and the primary supply vessels were determined. The subdermal layer in which the vessels lie and the course of the vessels were also investigated. RESULTS: The main blood supply source of the nasal tip proved to be the lateral nasal artery in 78% (80/102) of the cases examined, while the remaining cases (22%) received their blood supply via the dorsal nasal artery. Columellar branches were narrow in diameter and varied in size and appearance, and were therefore appeared insufficient as a main blood supply. These arteries passed through the musculoaponeurotic layer, but they were also in close proximity to the main surgical plane in the dome of the lower lateral cartilage. CONCLUSIONS: The authors speculate that the nasal tip blood supply in Asians is primarily derived from the lateral nasal or dorsal nasal arteries, with a variable contribution from the columella arteries. Therefore, it is important to correctly determine the surgical plane below the musculoaponeurotic layer in order to prevent skin flap necrosis or nasal tip deformity that may occur from damage to the main vessel during an external rhinoplasty approach.

Fontanelle and uncinate process in the lateral wall of the human nasal cavity.

OBJECTIVES: Although a complete anatomic knowledge of the fontanelle is a prerequisite to perform a surgical antrostomy opening, little is known about the boundary, shape, and size of the fontanelle. The purpose of this paper is to determine the best site for maintaining the patency of a surgical antrostomy opening by defining the anatomic boundaries, shape, and size of the fontanelle as well as its histological structure. MATERIALS AND METHODS: One hundred sagittally divided heads were utilized. Mucosa overlying the lateral nasal wall was carefully removed with an operating microscope under 6x magnification. In some cases, a double mucous membrane, including the posteroinferior portion of the uncinate process, was cut as a whole and embedded in paraffin. The sections were stained with H&E. RESULTS: The boundary of the fontanelle and the location of the natural ostium were described in detail. Eight patterns of the posteroinferior portion of the uncinate process were observed. There were three major fontanelle shapes when observed from the medial aspect to the lateral: triangular, pencil-like, and oval. The triangular type was the most common. The anterior portion of the fontanelle was shorter than the posterior when observed medially and was wider than the posterior portion when observed inferiorly. CONCLUSIONS: The anterior portion of the fontanelle is more prone to stenosis than the posterior portion. An antrostomy in the posterior fontanelle may be more ideal for a middle meatal antrostomy of the maxillary sinus.

Inhibitory effects of the root cortex of Paeonia suffruticosa on interleukin-8 and macrophage chemoattractant protein-1 secretions in U937 cells.

In an effort to elucidate the mechanism of the anti-inflammatory effect of mudanpi, the root cortex of Paeonia suffruticosa Andrews (Ranunculaceae), we determined the effects of the methanolic extract of mudanpi (MEM) on the secretions of interleukin (IL)-8, a major mediator of acute neutrophil-mediated inflammation, and macrophage chemoattractant protein (MCP)-1, a major mediator of chronic macrophage-mediated inflammation, in human monocytic U937 cells stimulated with phorbol myristate acetate (PMA). MEM significantly inhibited PMA-induced secretions of IL-8 and MCP-1 proteins in a dose-dependent manner. The inhibition of these chemokines by MEM was due to its suppression of IL-8 and MCP-1 genes. In addition, 1,2,3,4,6-penta-O-galloyl-beta-D-glucose, one of major constituents isolated from MEM, inhibited PMA-induced secretions of IL-8 and MCP-1 proteins by its suppression of IL-8 and MCP-1 genes. Thus, one possible anti-inflammatory mechanism of mudanpi, an anti-inflammatory Chinese crude drug, may be to inhibit the secretions of inflammatory chemokines.

Branching patterns and symmetry of the course of the facial artery in Koreans.

The topography and the course of the facial artery were investigated in 47 Korean cadavers. The final branch of the facial artery was the lateral nasal branch in 44.0% whereas it was the angular branch in 36.3% of the cases. In 54.5% of the cases, the facial artery ended symmetrically. According to previous studies, variations in the distribution pattern of the facial artery have been regarded as racial difference. However, in this study we showed that the diverse pattern of the facial artery distribution demonstrates individual variation rather than racial difference. The superior and inferior labial arteries on the right side were more dominant than those on the left. The average distance between the branching points for the inferior alar branch and for the lateral nasal branch was 15.9 mm, and it was 25.2 mm between the points for the superior labial branch and for the inferior alar branch. The branching point of the inferior labial branch was 30.9 mm apart on average from that of the superior labial branch. The courses of the facial arteries showed no significant differences based on either laterality or gender.

Emerging patterns of the cervical cutaneous nerves in Asians.

Numerous reports exist upon clinical viewpoints of the four cervical cutaneous nerves. Unfortunately, a detailed description of the cervical cutaneous nerves has not yet been published. For this reason, administering effective anaesthesia to a particular nerve branch is difficult. The aim of this study was to clarify the anatomical knowledge about the emerging patterns of the cervical cutaneous nerves in the superficial neck using 35 Korean cadavers (22 male, 13 female). Four cervical cutaneous nerve branches penetrating the fascia of the posterior border of the sternocleidomastoid muscle (SCM) were classified into seven types based on the locations of their nerve emergence. Among these, the separated type (L-G-T-S) was the most frequent (50%). followed by the L-G x T-S type (20.3%), in which the great auricular nerve (G) and the transverse cervical nerve (T) emerged at the same level on the posterior SCM border.