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Changes in the response of neutrophils to endotoxin priming following major abdominal surgery.

Endotoxin (ETX) primes polymorphonuclear cells (PMNs) for the subsequent release of reactive oxygen species (ROS) in response to various stimulants such as phorbol myristate acetate (PMA). Although PMNs contribute to oxidative stress after stimulation by standard stimulants and after priming by many humoral factors, it is unknown whether the PMNs from patients at different postoperative times exhibit the same response to the same standard stimulant. We examined the response of PMA-induced production of ROS from PMNs at various intervals after major abdominal surgery in response to ETX priming. This study was a prospective clinical and laboratory study conducted over a 7-day period that involved 25 patients who were referred for elective major abdominal surgery (8 for gastric cancer, 9 for colonic cancer, 8 for rectal cancer). Blood was sampled on the day before operation and on postoperative days (PODs) 1, 3, and 7. For each sample we measured luminol-dependent chemiluminescence (CL), the time to peak counts (Tmax) of PMNs stimulated by PMA, and the serum ETX level. We studied the correlation between CL and ETX in samples from PODs 1 and 3. We also studied the CL of PMNs on PODs 1 and 3 preincubated (primed) with various concentrations of ETX (0, 20, 40, 60, and 100 pg/ml). We found that CL decreased on POD 1 compared with the preoperative level (p <0.05) because of the decreased Tmax. The level of CL per 1 ml of whole blood, however, was higher on PODs 1 and 3 than preoperatively. During this time, leukocytosis should compensate for the impaired production of ROS by an individual PMN. The serum ETX level was increased on POD 1 (p <0.05). There was a negative correlation between CL and ETX on POD 1 (correlation coefficient ?0.62, p < 0.01) and a positive correlation on POD 3 (0.61, p <0.01). CL on POD 3 was accelerated by ETX priming, but the CL on POD 1 was depressed by the priming using a low concentration of ETX. The mode of the response of PMNs to ETX priming differed between PODs 1 and 3. On POD 1 the responses of PMNs to environmental stimulants is suppressed, but by POD 3 these responses had increased.

Digestive System Surgical Procedures↗

Enhanced peroxidase activity in rice leaves in response to excess iron, copper and zinc.

The effect of excess Fe(2+) on the peroxidase (POD) activity in detached rice leaves was investigated. FeSO(4) was effective in stimulating POD activity in detached rice leaves under both light and dark conditions. FeSO(4) but not K(2)SO(4) induced POD activity, indicating that POD activity is induced by Fe(2+). FeSO(4)-induced POD activity is not specific for the rice cultivar used in this study. CuSO(4) and ZnSO(4) were also observed to induce POD activity in detached rice leaves. Cycloheximide blocked the enhanced activity of POD by Fe(2+), Cu(2+) or Zn(2+), indicating de novo biosynthesis of the enzyme. Paraquat treatment resulted in a decrease in POD activity. H(2)O(2) had no effect on POD activity in detached rice leaves. It seems that Fe(2+)-, Cu(2+)- or Zn(2+)-induced POD may not be mediated by free radicals. Using isoelectric focusing to separate POD, it was found that excess Fe(2+), Cu(2+) or Zn(2+) induced both quantitative and qualitative metal-specific changes in POD isozyme pattern in detached rice leaves. A new POD isozyme with a pI of 4.81 can be induced by Fe(2+), Cu(2+) and Zn(2+) in detached rice leaves.

Journal Article↗

Comparison of two benzodiazepines used for sedation of children undergoing suturing of a laceration in an emergency department.

OBJECTIVES: (1) To determine if oral diazepam (POD) is as effective in sedating children less than 6 years of age for laceration repair as oral midazolam (POM) or intranasal midazolam (INM); and (2) To determine if patients stayed longer in the department after sedation when given POD for sedation. DESIGN/METHODS: Block-randomized, single-blind trial. SETTING: Tertiary pediatric emergency department. PARTICIPANTS: Patients 1 to 5 years old with a laceration requiring sutures were enrolled. INTERVENTIONS: All patients had topical anesthetic applied to the wound and were randomly assigned to POD 0.5 mg/kg, POM 1.0 mg/kg, or INM 0.4 mg/kg for sedation. RESULTS: One hundred twenty-nine patients were enrolled, 42 POD, 45 POM, and 42 INM. Each group was similar at baseline for age, heart rate, respiratory rate, blood pressure, oxygen saturation, previous laceration or sedation, anxiety score, and site of laceration. POM and POD were better tolerated than INM (P = 0.05 and 0.034), respectively. Time to sedation was significantly longer in POD (31.0 +/- 9 min) than INM (26.1 +/- 9 min) (P = 0.011) but there was no significant difference when comparing the other groups. However, this difference was not clinically significant. POD was significantly worse at sedating children compared with POM and INM on all four scores (ie, doctor, nurse, parent, and investigator), but INM and POM were equivalent. Total time in the department was no different between POM and INM or POM and POD, but was significantly different for POD (53.9 +/- 16 min) and INM (48 +/- 12 min); however, this difference was minimal. More patients were said to be drowsy at home in the POM group (51%) than the POD group (32%). CONCLUSIONS: The oral route of delivery of POM and POD was better tolerated than INM. POM and INM were more effective at sedation than POD, but there was no clinical difference between any groups for time to sedation or time to discharge. More patients in the POM group had side effects after leaving the department. POD may be an alternative to POM, but a higher dose may be required, possibly with longer recovery times.

Child, Preschool↗

Changes in coagulatory profile after orthopedic surgery.

Platelet count, prothrombin time (PT), partial thromboplastin time (PTT) and fibrinogen concentrations were prospectively evaluated in 65 patients undergoing orthopedic surgery at the National Cheng-Kung University Hospital between June 1990 and February 1991. All patients were hospitalized for at least 7 days after surgery. Coagulation data were collected preoperatively and on the first, third and seventh postoperative days (POD 1, 3, 7). The average estimated blood loss was 374 mL (range, 25-2.350 mL). Stored whole blood transfusion of 2 to 5 units (1 unit = 250 mL) was required by 12 patients. A further 12 patients received a transfusion of two to six units of packed red cells. Platelet count decreased to the lowest level on POD 1, recovered to normal on POD 3 and was even greater by POD 7. PT was prolonged on POD 1, recovered by POD 3 and remained stable on POD 7. PTT was prolonged on POD 1, became more prolonged on POD 3 and returned to normal by POD 7. Fibrinogen concentrations were not significantly altered on POD 1, but increased above the preoperative level on POD 3 and returned gradually to normal by POD 7. Variables such as age, sex, type of operation and duration of tourniquet did not affect these patterns. There was a positive correlation between duration of surgery, net blood loss and decrease in platelet count. This study examined some of the physiologic coagulatory variations after orthopedic surgery. Recognition of these patterns might lead to better clinical judgment when perioperative coagulatory disorders are suspected.

Adolescent↗

Podophyllotoxin-loaded solid lipid nanoparticles for epidermal targeting.

The purpose of this study was to evaluate solid lipid nanoparticles as the topical carrier for epidermal targeting of podophyllotoxin (POD). The high pressure homogenization was employed to prepare drug-loaded solid lipid nanoparticles. The POD-loaded SLN stabilized by 0.5% poloxamer 188 and 1.5% soybean lecithin (P-SLN) and 2% polysorbate 80 (T-SLN) was characterized by photon correlation spectroscopy (PCS). P-SLN showed an average diameter of 73.4 nm and a zeta potential of -48.36 mV. The imaging of AFM indicated that the P-SLN had a spherical shape. DSC and X-ray diffraction analysis showed that POD was dispersed in SLN in an amorphous state. The in vitro permeation study showed that P-SLN increased the accumulative amount of POD in porcine skin 3.48 times over 0.15% tincture. But T-SLN with a diameter of 123.1 nm and a zeta potential of -17.4 mV did not show a high accumulative amount of POD when compared with P-SLN, though both P-SLN and T-SLN could avoid the systemic uptake of POD. Because of the fluorescence property of POD, fluorescence microscopy imaging was employed to visualize the penetration of POD into skin from SLN. The penetration of POD from P-SLN seemed to follow two pathways along the stratum corneum and hair follicle route. The imaging revealed that P-SLN had a strong localization of POD within epidermis. The penetration of P-SLN with low particle size into stratum corneum along the skin surface 'furrow' and the consequent controlled release of POD might lead to the epidermal targeting. P-SLN provides a good epidermal targeting effect and may be a promising carrier for topical delivery of POD.

Animals↗

Removal of urinary catheter on postoperative day 3 or 4 after radical retropubic prostatectomy.

OBJECTIVES: To determine the feasibility and safety of removing the urinary catheter on postoperative day (POD) 3 or 4 after radical retropubic prostatectomy (RRP). METHODS: Between January 2001 and August 2001, gravity cystography was performed on POD 3 or 4 after RRP by a single surgeon (H.L.) on 151 men. The urinary catheter was removed on POD 3 or 4 providing no extravasation was evident on cystography. Urinary catheters were replaced over a guidewire placed into the bladder under flexible cystoscopic guidance in cases of acute urinary retention (AUR). Continence was assessed at 3 months after RRP. RESULTS: Of the 151 cystograms performed on POD 3 or 4, 116 (76.8%) revealed no evidence of extravasation. The indwelling catheters were removed in 114 of these cases (98.3%). Twenty-two (19.3%) of the 114 men whose catheters were removed on POD 3 or 4 developed AUR within 48 hours of catheter removal, requiring catheter replacement. Two of these patients required repeated surgery secondary to complications related to AUR. At 3 months after RRP, 75% of the men whose catheters were removed on POD 3 or 4 required no pads or a single pad during a 24-hour interval, and 77.6% reported none or slight bother from incontinence. Of the 37 men whose catheters were removed on POD 7 or later, 1 patient (2.7%) developed AUR, and the catheter was replaced without complications. At 3 months after RRP, 65.7% of men whose catheters were removed on POD 7 or later required no pads or a single pad during a 24-hour interval, and 71.4% reported none or slight bother from incontinence. The incidence of anastomotic stricture in men whose catheters were removed on POD 3 or 4 and POD 7 or later was 12.1% and 22.6%, respectively. CONCLUSIONS: Most men will have a watertight anastomosis on POD 3 or 4 after RRP. Early catheter removal does not have a negative impact on continence or the rate of anastomotic strictures. Because of the high incidence of AUR, requiring replacement of the urinary catheter, and the potential for disruption of the anastomosis or bladder neck reconstruction, we currently recommend delaying catheter removal until POD 7 or later.

Anastomosis, Surgical↗

Patients' perception of recovery after third molar surgery.

PURPOSE: This study evaluated patients' perceptions of recovery after third molar surgery. METHODS: Two hundred forty-nine patients (age 13 to 37 years) at 2 clinical centers were enrolled in a prospective study before the surgical removal of third molars. Each patient was given a 21-item Health-Related Quality of Life instrument (HRQOL) to be completed each postoperative day (POD) for 14 days. The instrument was designed to assess patients' perception of recovery: pain, oral function, general activity measures, and other symptoms. Pain dimensions were recorded with a 7-point Likert-type scale; all other conditions were measured on 5-point Likert-type scales. The impact of each predictor variable such as age, gender, and length of surgery on recovery was assessed with Cochran-Mantel-Haenszel statistics, controlling for clinical center. RESULTS: After the 14-day postoperative period, 201 of the original 249 patients returned the completed HRQOL instrument; the 48 patients who did not return their diary had third molar conditions and surgery similar to the 201 patients who responded. On POD 1, 63.5% of patients reported their worst pain as severe (score, 5 to 7/7) at some time during the day. By POD 7, only 15% of patients reported their worst pain as severe. Average pain levels were much less; 29% reported their average pain as severe (score, 5 to 7/7) on POD 1, decreasing to 5.5% by POD 7. Patients experienced substantial interference in oral function; chewing, 85%; mouth opening 78.5%, and speaking 37.5% on POD 1. By POD 6, oral function had improved; chewing, 19%, mouth opening, 15%; and speaking, 1.5%. General measures also were affected on POD 1; social activity, 61.5%; recreation, 70.5%; and daily routine, 60%. Patients assumed a more normal lifestyle by POD 5. Swelling seemed to be at its maximum on PODs 1 and 2 (day 1, 53%; day 2, 61%) and decreased markedly by POD 5 (10%). Food collection in the surgical sites posed the biggest problem for patients on POD 9 (20%). Age was not a predictor of prolonged recovery. However, surgery time 30 minutes or longer, or having all third molars below the occlusal plane, did prolong recovery. Females also reported a longer recovery period. CONCLUSIONS: This information is valuable to patients deciding on third molar surgery and to clinicians providing informed consent.

Adolescent↗

Intestinal permeability in patients after surgical trauma and effect of enteral nutrition versus parenteral nutrition.

AIM: To study the intestinal permeability (IP) following stress of abdominal operation and the different effects on IP of enteral nutrition (EN) and parenteral nutrition (PN). METHODS: Forty patients undergoing abdominal surgery were randomized into EN group and PN group. Each group received nutritional support of the same nitrogen and calorie from postoperative day (POD) 3 to POD 11. On the day before operation (POD-1), POD 7 and POD 12, 10 g of lactulose and 5 g of mannitol were given orally, and urine was collected for 6 hours. Urine excretion ratios of lactulose and mannitol (L/M) were measured. RESULTS: L/M ratios of EN group on POD-1, POD 7 and POD 12 were 0.026+/-0.017, 0.059+/-0.026, 0.027+/-0.017, respectively, and those of PN group were 0.025+/-0.013, 0.080+/-0.032, 0.047+/-0.021, respectively. Patients of both groups had elevated L/M ratios on POD 7 vs. POD-1. However the ratio returned toward control level in EN group by POD 12. In contrast, PN group still had elevated L/M ratios on POD 12. CONCLUSION: L/M ratio increases for a period of time after surgical trauma and the loss of gut mucosal integrity can be reversed by substitution of enteral nutrition.

Adult↗

Low-pH-sensitive poly(ethylene glycol) (PEG)-stabilized plasmid nanolipoparticles: effects of PEG chain length, lipid composition and assembly conditions on gene delivery.

BACKGROUND: We have studied the effects of the poly(ethylene glycol) (PEG) chain length and acyl chain composition on the pH-sensitivity of acid-labile PEG-diorthoester (POD) lipids. The optimal conditions are described for preparation of DNA plasmid encapsulated POD nanolipoparticles (NLPs) which mediate high gene delivery activity in vitro with moderate cytotoxicity. METHODS AND RESULTS: A series of POD lipids with various PEG chain lengths (750, 2000, and 5000 Da) or acyl chains (distearoyl 18:0 or dioleoyl 18:1) were incorporated into DNA containing NLPs or model liposomes as a stealth and bioresponsive component. We investigated the collapse kinetics of the POD-stabilized liposomes when the PEG chain length was changed. We optimized a detergent dialysis method to encapsulate plasmid DNA into NLPs prepared from a mixture of the various POD lipids, cationic lipid and phosphatidylethanolamine lipid. A critical concentration (28 mM) of n-octyl-beta-D-glucopyranoside (OG) enabled high encapsulation of DNA plasmid into 100 nm particles with a neutral surface charge. The POD NLPs are stable at pH 8.5 but rapidly collapse (approximately 10 min) into aggregates at pH 5.0. In the detergent solution there is a metastable DNA-lipid intermediate that evolves into a stable NLP if the detergent is removed shortly after adding DNA to the lipid-detergent mixture. The rank order of transfection activity from NLPs containing PEG-lipid was POD 750 > POD 5000 = POD 2000 > non-pH-sensitive PEG-lipid. The particle size stability was in the reverse order. Binding of the NLPs to cells reached a maximum level by 12 hours. The POD NLPs had slightly less transfection activity but considerably lower cytotoxicity than the PEI-DNA polyplex. CONCLUSIONS: Of the PEG-orthoester lipids tested, POD 2000 is the better choice for the preparation of sterically stabilized NLPs with a small particle diameter, good stability, low cytotoxicity, and satisfactory transfection activity.

Animals↗

Seed Development in Phaseolus vulgaris L. cv Seminole: I. Developmental Independence of Seed Maturation.

Phaseolus vulgaris L. cv Seminole pods removed from the plant continued their development when incubated in suitable conditions. Seeds continued to grow and develop and pods and seeds passed through an apparently normal developmental sequence to dryness. Seed growth was at the expense of pod dry weight (DW) reserves. Losses of pod DW paralleled DW gains by seeds in detached pods and in pod cylinders containing a seed. The transfer activity was apparent only within the period 10 to 30 days after anthesis (DAA) with maximal activity between 15 to 20 DAA. This period corresponds to maximum pod growth and the attainment of maximal DW. Seeds are in only the early phase of seed growth at this time. No DW transfer was observed at developmental stages beyond 30 to 35 DAA when normal senescence DW losses in pods became evident and seeds were in the later phase of seed fill. Pods or pod cylinders remained green and succulent over the transfer period, later passing through yellowing and drying phases characteristic of normal development. DW transfer was dependent on funicle integrity and was readily detectable in pod cylinders after 7 days incubation. The DW transfer activity may contribute to continuing nutrition of seeds under conditions where the normal assimilate supply to seeds becomes limiting. Defoliation and water stress treatments applied to Phaseolus plants reduced seed yields but allowed persistence of seed maturation processes such that all seeds developing to dryness were capable of germination.

Journal Article↗

Ultrastructural and Immunocytochemical Studies on the H(2)O(2)-Producing Enzyme Pyranose Oxidase in Phanerochaete chrysosporium Grown under Liquid Culture Conditions.

The ultrastructural distribution of the sugar-oxidizing enzyme pyranose 2-oxidase (POD) in hyphae of Phanerochaete chrysosporium K-3 grown under liquid culture conditions optimal for the enzyme's production was studied by transmission electron microscopy immunocytochemistry. Using the 3-dimethylaminobenzoic acid-3-methyl-2-benzothiazolinone hydrazone hydrochloride H(2)O(2) peroxidase spectrophotometric assay, POD was detected in mycelial extracts from days 7 to 18, with maximum activity recorded on day 12. Onset of POD activity occurred in the secondary phase of hyphal development at a time of stationary growth, glucose limitation, and pH increase. POD was also detected extracellularly in the culture fluid from days 7 to 18, with maximum activity recorded on day 13. At early stages of development (3 to 4 days), using anti-POD antibodies and immunogold labeling, POD was localized in multivesicular and electron-dense bodies and in cell membrane regions. After 10 to 12 days of growth, at maximum POD activity, POD was concentrated within the periplasmic space where it was associated with membrane-bound vesicles and other membrane structures. At later stages of development (17 to 18 days), when the majority of hyphae were lysed, POD was observed associated with residual intracellular membrane systems and vesicles. Transmission electron microscopy immunocytochemical studies also demonstrated an extracellular distribution of the enzyme at the stationary growth phase, showing its association with fungal extracellular slime. In studies of ligninolytic cultures of the same fungus, POD was found to have a similar intracellular and extracellular distribution in slime as that recorded for cultures grown with cornsteep. POD's peripheral cytoplasmic distribution shows similarities to the cellular distribution of that reported previously for H(2)O(2)-dependent lignin and manganese peroxidases in P. chrysosporium.

Journal Article↗

Detection of pathogen transmission in neonatal nurseries using DNA markers as surrogate indicators.

OBJECTIVE: Nosocomial infections are a major problem confronting neonatal intensive care units (NICUs). This study was conducted to determine if DNA markers designed from the cauliflower mosaic virus (CaMV 35S DNA) can serve as surrogate indicators of nosocomial pathogen transmission in NICUs. METHODS: Regions of cauliflower CaMV 35S promoter DNA were designed to serve as surrogate markers of microbial transmission pathways. Each of 6 pods within the NICU under study houses 8 newborn infants. DNA marker was placed on the telephone handle in only 1 of the 6 NICU pods (study pod). Bedside caregivers were blinded as to when placebo or marker were placed in the pod. Thirty-two samples were collected from predetermined sites within each pod at 0, 4, 8, 24, and 48 hours and 7 days after DNA placement. Similar sites were sampled in each of the 6 pods. Additional samples were collected concurrently from areas of the NICU segregated from direct patient care. Polymerase chain reactions were performed on collected samples, and products were analyzed by agarose gel electrophoresis. RESULTS: One thousand three hundred samples of the environment and hands of personnel were collected and analyzed. Within the study pod, 58% of sites tested positive for the DNA marker throughout all time points; positive sites peaked at 8 hours (78%) and declined to 23% positive at 7 days. The other 5 pods had a mean of 18% of sites positive throughout the 7 days and exhibited a similar decline throughout time. The most consistently positive sites within all pods were the blood gas analyzers, computer mice, telephone handles, medical charts, ventilator knobs, door handles, radiant warmer control buttons, patient monitors, and personnel hands. In areas outside the pods, the nurse's station, resident physician charting area, changing room, and staff break room had a mean of 50% positive sites throughout all time points. CONCLUSIONS: DNA markers proved useful as safe, surrogate indicators of microorganism transmission within and outside pods in the NICU. We speculate that utilization of these techniques in the hospital environment will provide important information about transmission of pathogens in the NICU, assist in developing and enforcing cleaning procedures, and permit testing of educational intervention programs targeting a decrease in nosocomial infections.nosocomial infection, neonatal intensive care, DNA marker, polymerase chain reaction, infection control.

Caulimovirus↗

Involvement of CYP2E1 as A low-affinity enzyme in phenacetin O-deethylation in human liver microsomes.

Phenacetin O-deethylation (POD) exhibits biphasic kinetics in human liver microsomes. Although cytochrome P-450 (CYP) 1A2 is responsible for the high-affinity component of POD, the enzyme(s) that catalyzes the low-affinity reaction is still unknown. We examined the roles of human CYPs in POD by using human liver microsomes and recombinant CYPs from baculovirus-infected insect cells. Of the recombinant CYPs studied, CYP1A2 showed the highest POD activity. CYP1A1, CYP2C19, CYP2D6, CYP2E1, and CYP3A4 also showed POD activity at 500 microM phenacetin. K(M) values of recombinant CYP1A2 and CYP2E1 (28 +/- 2 microM and 785 +/- 125 microM, respectively) were similar to those of the high- and low-affinity components of POD in pooled human liver microsomes (15 +/- 5 and 894 +/- 189 microM, respectively). Fluvoxamine (10 microM) and anti-CYP1A2 antibodies potently inhibited POD activity at 500 microM phenacetin in pooled human liver microsomes to 22.8 and 34.2% of controls, respectively. CYP2E1 inhibitors diethyldithiocarbamate and aniline also reduced POD activity. The combination of fluvoxamine (10 microM) and aniline (1 mM) further inhibited the residual POD activity not inhibited by fluvoxamine alone. Microsomal POD activity in 12 human livers in the absence of fluvoxamine was correlated with immunoquantified CYP1A2 levels (r = 0.961, p <.001) and, in the presence of 10 microM fluvoxamine, was correlated with immunoquantified CYP2E1 levels (r = 0.589, p <.01) or chlorzoxazone 6-hydroxylase activity (r = 0.823, p <.001). These results suggest that CYP2E1 is responsible for the low-affinity component of POD in human liver microsomes.

Analgesics, Non-Narcotic↗

Up-regulated intragraft gene expression, ICAM-1 and IL-2R molecules, and apoptotic epithelial cells during rejection of rat small intestine allografts.

OBJECTIVE: To investigate the kinetics and the magnitude of intragraft gene expression of interleukin-2 (IL-2), interferon-gamma (IFN-gamma), perforin and granzyme B, and intragraft expression of interleukin-2 receptor (IL-2R) and intercellular adhesion molecule-1 (ICAM-1) during acute rejection episodes, and to analyze the changes in apoptosis in small intestinal allograft rejection. METHODS: Heterotopic small intestine transplantation was performed with inbred rats F344/N (RT1l) and Wistar/A (RT1-Ak, RT1-Ed). All recipients were divided into four groups: group 1: Wistar, native control; group 2: Wistar-->Wistar; group 3: F344-->Wistar and group 4: F344-->Wistar + cyclosporine A (6 mg.kg-1.d-1 i.m.). The grafts were harvested on postoperative days (PODs) 3, 5 and 7. All samples were examined pathologically. Intragraft mRNA expression of IL-2, IFN-gamma, perforin and granzyme B were detected with reverse transcriptase polymerase chain reaction (RT-PCR) and intragraft expression of IL-2R and ICAM-1 were stained using immunohistochemistry. We also analyzed the change in apoptosis rejection with terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL). RESULTS: Mild acute rejection occurred on POD 3 in the allograft group, moderate acute rejection on POD 5, and severe acute rejection on POD 7, while none of the isografts had histological evidence of acute rejection. Cyclosporine A could effectively control rejection. Gene expression was virtually negative in the native control. Only on POD 5 was IL-2 mRNA expression of allografts significantly higher than that of isografts (P < 0.05). IFN-gamma mRNA expression was significantly higher than that of the control groups (P < 0.01) on PODs 3, 5 and 7, and the level of perforin and granzyme B mRNA expression reached significantly higher levels than in the other two control groups on POD 5 and POD 7. Intragraft IL-2R expression of the allograft was significantly higher than that of the other three control groups. Only on POD 3 was intragraft ICAM-1 expression of allografts significantly higher than isografts. The number of apoptotic cells per crypt of allografts was significantly higher than that of the other three control groups on POD 3 and POD 5 (P < 0.01). CONCLUSION: Transcription of IL-2, IFN-gamma, perforin and granzyme B, and expression of IL-2R and ICAM-1 as well as apoptosis of epithelial cells of the grafts play an important role in small intestine allograft rejection. Intragraft gene expression of IFN-gamma and intragraft expression of IL-2R as well as apoptotic epithelial cells may become a specific and sensitive diagnostic method of clinical value. Furthermore, therapeutic strategies to alter these molecules in small intestine transplantation may improve the outcome of current antirejection therapy.

Animals↗

Perioperative hemodynamic study of patients undergoing abdominal surgery using pulse dye densitometry.

BACKGROUND/AIMS: Pulse dye densitometry (PDD) using indocyanine-green (ICG) is a newly developed technique for monitoring cardiac output (CO), cardiac index (CI), circulating blood volume (BV) and ICG elimination rate (K-ICG). We measured hemodynamic changes during the perioperative period in patients undergoing digestive surgery to analyze relationships between hemodynamic changes and surgical procedures, blood loss, water balance and SIRS. METHODOLOGY: Eighty-seven patients who underwent gastrectomy (n=46) and colectomy (n=41) without postoperative complications were enrolled in this study. The corresponding data from 15 patients who underwent laparoscopic cholecystectomy were used as controls. CO, CI, BV and K-ICG were measured by PDD before operation, on the first postoperative day (POD 1), POD 3, POD 7 and POD 14. RESULTS: In all patients, CO and CI increased significantly until POD 3 compared with preoperative levels. BV on POD 1 decreased significantly compared to the preoperative level. K-ICG increased significantly until POD 14. Laparoscopic cholecystectomy resulted in less surgical stress than gastrectomy or colectomy as measured by hemodynamic changes. There were minimal differences in hemodynamics between the gastrectomy and colectomy groups. There were significant negative correlations between intraoperative blood loss and the [POD 1: preoperative values] ratios for CO, CI, BV or K-ICG. There was no correlation between changes in water balance from operation to POD 1 and [POD 1: preoperative value] BV ratio. CONCLUSIONS: An increase in CO and decrease in BV were observed at the early operative stage, especially in patients with systemic inflammatory response syndrome (SIRS). Interestingly, hepatic artery flow volume (K-ICG) remained high until POD 14. It is important to minimize intraoperative blood loss, since it markedly affects postoperative hemodynamics.

Abdomen↗

Concordant lung xenograft rejection in a hamster-to-rat model.

This study was conducted to investigate the functional and morphological aspects of orthotopic lung xenograft rejection in a concordant hamster-to-rat donor-recipient species combination. By postoperative day (POD) 3, allotransplanted grafts demonstrated good aeration, but infiltrates were seen in all the xenotransplanted lungs. Antihamster lymphocytotoxic antibody titers increased to 5.2 +/- 1.1 by POD 3 (P < 0.05 vs POD 1) and reached 7.0 +/- 0.8 by POD 5 (P < 0.05 vs PODs 1 and 3). The CD4+/CD8+ ratio in peripheral blood lymphocytes increased significantly on POD 3 (P < 0.05 vs untransplanted), but decreased by POD 5 (P < 0.05). Histologically, on POD 3 the xenotransplanted grafts were characterized by perivascular cellular infiltrates and edema. Cytologically, the cells consisted of small round lymphocytes, monocytes, and occasional neutrophils. Immunohistochemical analysis showed heavy IgM and C3 deposits in the vascular endothelium, without any IgG deposits. Allotransplanted grafts showed moderate W 3/25 + (28.3 +/- 17.3%) and MRC OX8 + (38.7 +/- 0.7%) cellular infiltrations on POD 3, but ED1 + (8.0 +/- 3.7%) cells were rare. Conversely, in the xenotransplanted grafts, ED1 + (34.2 +/- 16.4%) cells were more prevalent than MRC OX8 + (18.1 +/- 16.5%) cells on POD 3, at P < 0.01 and P < 0.05 vs allograft, respectively. These results indicate that both antidonor antibodies and macrophages/monocytes play an important role in the concordant lung xenograft rejection.

Animals↗

Influence of thoracic epidural analgesia on cardiovascular autonomic control after thoracic surgery.

BACKGROUND: Thoracic epidural analgesia (TEA) is effective in alleviating pain after major thoracoabdominal surgery and may also reduce postoperative mortality and morbidity. This study investigated cardiovascular autonomic control in patients undergoing elective thoracic surgery and its modulation by continuous TEA. METHODS: Thirty-eight patients were randomly assigned to receive patient-controlled analgesia (PCA group) or thoracic epidural analgesia (TEA group) with doses of bupivacaine (0.25% during operation, 0.125% after operation) and fentanyl (2 microg ml(-1)). Heart rate variability (HRV), baroreflex function and pressure response to nitroglycerine and phenylephrine were assessed before operation, 4 h after the end of surgery (POD 0) and on the first and second postoperative days (POD 1 and POD 2). RESULTS: Early after surgery, all HRV variables and baroreflex sensitivities were markedly decreased in both groups. In the TEA group, total HRV and its high-frequency components (HF) increased towards preoperative values at POD 1 and POD 2, whereas the ratio of low to high frequencies (LF/HF) was significantly reduced (mean (SD), -44 (15)% at POD 0, -38 (17)% at POD 1, -37 (18%) at POD 2) and associated with blunting of the postoperative increase in heart rate and blood pressure. In the PCA group, the ratio of LF/HF remained unchanged and the decrements in HRV variables persisted until POD 2. In the two groups, baroreflex sensitivities and pressure responses recovered preoperative values at POD 2. CONCLUSIONS: In contrast with PCA management, TEA using low concentrations of bupivacaine and fentanyl blunted cardiac sympathetic neural drive, resulting in vagal predominance, while HRV variables were better restored after surgery.

Adult↗

Factors relating to coagulation, fibrinolysis and hepatic damage after liver resection.

A survey of the blood of twenty-two patients who had undergone hepatic resection was performed. Serum levels of alpha-2 plasmin inhibitor-plasmin complex initially decreased from 1.58 +/- 0.31 microgram/ml on the preoperative day (PREOP), to 0.92 +/- 0.14 mu/ml on the first postoperative day (POD 1), and then increased to 3.13 +/- 0.92 micrograms/ml on the seventh postoperative day (POD 7) (mean +/- SE)). Thrombin-anti-thrombin III complex (14.2 +/- 4.3 ng/ml on PREOP and 26.0 +/- 4.1 ng/ml on POD 7 (mean +/- SE)) and D-dimer (335 +/- 96 ng/ml on PREOP and 1859 +/- 258 ng/ml on POD 7 (mean +/- SE)) increased in the early postoperative stage. The level of 6-keto-prostaglandin F1 alpha increased after the operations (from 13.2 +/- 1.8 pg/ml on PREOP to 37.8 +/- 12.8 pg/ml on POD 7 (mean +/- SE)). The level of thromboxane B-2 decreased at first, and then gradually increased and returned to its preoperative level on POD 7 (144.7 +/- 43.8 pg/ml on PREOP, 57.6 +/- 27.5 pg/ml on POD 1 and 152.5 +/- 58.4 pg/ml on POD 7 (mean +/- SE)). Superoxide dismutase activity increased at first, and then gradually decreased, postoperatively (2.8 +/- 0.5 NU/ml on PREOP, 4.8 +/- 0.8 NU/ml on POD 1 and 2.6 +/- 0.3 NU/ml on POD 7 (mean +/- SE)). That is, biodefensive reactions which protect patients against the shift to disseminated intravascular coagulation (DIC) were inferred with by the increase in antiplatelet aggregation, despite the activation of coagulation and fibrinolytic mechanisms after hepatic resection.

Adult↗