Expression of regulatory T cell (Treg) activation markers in endometrial tissues from early and late pregnancy in the feline immunodeficiency virus (FIV)-infected cat.

Regulatory T cells (Tregs) support pregnancy maintenance by suppressing placental inflammation, while diminished Treg function may accompany reproductive failure. Experimental FIV infection frequently results in vertical transmission and increased pregnancy failure in the cat. The mechanism of reproductive compromise is unknown. We hypothesized that FIV infection alters endometrial Treg population dynamics and function, potentiating vertical transmission and reproductive failure. RNA collected from early and late gestation reproductive tissue and fetuses from FIV infected and control cats was probed for expression of FIV gag and Treg markers CD25, FOXP3, and CTLA4, using real time reverse-transcriptase (RT)-PCR. Frequent placental and fetal infection and reproductive failure were detected at early and late pregnancy. Expression of FOXP3 and CTLA4 was higher in early gestation tissues from control cats. FIV infection significantly reduced expression of FOXP3 and CTLA4 at early, but not late pregnancy. At late pregnancy, CTLA4 was expressed to higher levels in infected tissues. The number of tissues with decreased co-expression of FOXP3 and CTLA4 was significant in infected cats at early pregnancy. No significant changes in CD25 expression occurred between FIV-infected and control animals at early or late pregnancy. Differences in Treg marker expression were not significant between viable and non-viable pregnancies in infected cats. The detection of Treg markers in these feline tissues provides the first evidence of feline endometrial Tregs and suggests that such cells diminish as pregnancy progresses. These cells may be depleted or rendered less functional by viral infection, but understanding their role in pregnancy requires further study.

Changes in serum electrolytes during treatment of patients in liver failure with molecular adsorbent recirculating system.

PURPOSE: To study the effect of MARS on serum electrolytes during liver failure. DESIGN: Twenty-three patients admitted to a quaternary health care facility from September 2000 to May 2002, 22 adults and 1 child, 11 males (48%) and 12 females (52%), age 15-70 (median 53), treated with MARS for: 12 acute-on-chronic liver failure (52%); 4 fulminant hepatic failure (17%); 3 intractable pruritus (13%); 2 primary-non-function (9%); 2 following major liver resection (9%). PROCEDURES: Sodium, potassium, chloride, phosphorus, calcium, and magnesium were measured in the serum, ultrafiltrate and albumin circuit before and after MARS. STATISTICAL METHODS: A comparison of electrolyte concentrations, before and after MARS, was performed using a paired t test. MAIN FINDINGS: Serum electrolyte concentrations before and after MARS, while statistically significant in some cases, were very small, and of no clinical relevance. CONCLUSION: MARS exchanges potassium, chloride, calcium, and magnesium by ultrafiltration; sodium by the albumin dialysis.

Lactate levels in open interstitial thermal ablation for liver tumors.

Intraoperative radio frequency interstitial thermal ablation (RITA) may result in a reduction of the functional hepatic reserve. To assess this further, we evaluated perioperative lactate levels as a measure of hepatic dysfunction. Sixteen patients scheduled for open RITA (O-RITA) were enrolled in the study. Arterial lactate levels (mmol/L) were measured prior to tumor needle insertion (T0), after O-RITA completion (T1), after wound closure (T2) and 24 hrs after surgery (T3). Correlation between hemodynamic parameters including MAP, and CVP, at T0, T1, T2, T3 and the perioperative rate of lactate production were also analyzed. Total bilirubin, transaminases and international normalized ratio for prothrombin activity (INR) were measured preoperatively and postoperative at day 1, 2, 3 and 7. Data are expressed as mean +/- SD and analyzed with ANOVA. Additionally, the Duncan post hoc test was used for multiple comparisons of the differences in mean values. A p-value <0.05 was considered significant. Lactate levels did not increase significantly at time points specified above (P = NS). Similarly, hemodynamic parameters analyzed did not show any significant change at the different time points (P = NS). Total bilirubin and INR did not demonstrate statistically significant changes at the aforementioned time points. Serum transaminases peaked during the immediate postoperative period and normalized to preoperative values by one-week post surgery. These results demonstrate that O-RITA does not induce hyperlactatemia and does not reduce the functional residual liver parenchyma.

Correlation between peri-operative serum lactate levels and outcome in pancreatic resection for pancreatic cancer, preliminary report.

This study was undertaken in order to verify if peri-operative serum lactate level changes, resulting from manipulation of the splanchnic circulation during pancreatectomy, reflected clinical outcome in twenty patients (9 males-11 females age 33 to 76) operated for pancreatic cancer. Lactate levels were evaluated at the beginning of the procedure (T0), after surgical manipulation before pancreatic resection (T1), after resection (T2), and 24 hours post-op. (T3). Furthermore, to highlight possible hemodynamic instability that could contribute to altered lactate clearance, mean arterial pressure (MAP) and central venous pressure (CVP) were continuously monitored during the study period. Peri-operative mortality within 60 days after surgery, Intensive Care Unit (ICU) length of stay, and peri-operative complications were the main indicators investigated in order to evaluate the impact of serial lactate levels in this patient population. Hyperlactatemia observed peri-operatively during pancreatic resection for cancer is significantly correlated with peri-operative mortality and also with longer ICU length of stay. Though, due to the relatively small number of the patients, more extensive investigation is needed in order to confirm such interesting preliminary data.

Novel bioartificial liver support system: preclinical evaluation.

Preclinical safety and efficacy evaluation of a novel bioartificial liver support system (BLSS) was conducted using a D-galactosamine canine liver failure model. The BLSS houses a suspension of porcine hepatocytes in a hollow fiber cartridge with the hepatocytes on one side of the membrane and whole blood flowing on the other. Porcine hepatocytes harvested by a collagenase digestion technique were infused into the hollow fiber cartridge and incubated for 16 to 24 hours prior to use. Fifteen purpose-bred male hounds, 1-3 years old, 25-30 kg, were administered a lethal dose, 1.5 g/kg, of D-galactosamine. The animals were divided into three treatment groups: (1b) no BLSS treatment (n = 6); (2b) BLSS treatment starting at 24-26 h post D-galactosamine (n = 5); and (2c) BLSS treatment starting at 16-18 h post D-galactosamine (n = 4). While maintained under isoflurane anesthesia, canine supportive care was guided by electrolyte and invasive physiologic monitoring consisting of arterial pressure, central venous pressure, extradural intracranial pressure (ICP), pulmonary artery pressure, urinary catheter, and end-tidal CO2. All animals were treated until death or death-equivalent (inability to sustain systolic blood pressure > 80 mmHg for 20 minutes despite massive fluid resuscitation and/or dopamine administration), or euthanized at 60 hours. All animals developed evidence of liver failure at 12-24 hours as evidenced by blood pressure lability, elevated ICP, marked hepatocellular enzyme elevation with microscopic massive hepatocyte necrosis and cerebral edema, elevated prothrombin time, and metabolic acidosis. Groups 2b and 2c marginally prolong survival compared with Group 1b (pairwise log rank censored survival time analysis, p = 0.096 and p = 0.064, respectively). Since survival times for Groups 2b and 2c are not significantly different (p = 0.694), the groups were combined for further statistical analysis. Survival times for the combined active treatment Groups 2b and 2c are significantly prolonged versus Group 1b (p = 0.047). These results suggest the novel BLSS reported here can have a significant impact on the course of liver failure in the D-galactosamine canine liver failure model. The BLSS is ready for Phase I safety evaluation in a clinical setting.

The hepatopulmonary syndrome.

The hepatopulmonary syndrome is a disease entity seen in association with liver failure and other disease entities. It is a devastating consequence of liver failure that results in a significant morbidity for affected patients. Currently, there are no identified medications that ameliorate the symptoms of hypoxemia in this disease state. Recent research, however, has begun to unravel the pathobiology of the vascular dilations that arise in the lungs of patients with liver failure. In this article, a compendium of current knowledge is presented, as well as the contemporary methods for identifying and treating patients.

Morbidity and mortality in patients with coronary artery disease undergoing orthotopic liver transplantation.

Thirty-two patients with coronary artery disease who underwent liver transplantation between 1990 and 1994 were identified. Coronary artery disease was managed medically (n = 9), by angioplasty (n = 1), or surgically (n = 22) prior to liver transplantation. Two patients underwent simultaneous coronary artery bypass grafting and liver transplantation. Complete preoperative cardiac evaluation was performed in all patients. Perioperative and postoperative morbidity and mortality were retrospectively determined. Overall mortality was 50%, whereas morbidity was 81%. Follow-up was between 1 and 3 years after liver transplantation. Subgroup analysis revealed that medically managed patients had a 56% mortality and a 100% morbidity. The patient who underwent angioplasty survived without morbidity. One patient who underwent simultaneous coronary artery bypass grafting and liver transplantation died intraoperatively. The second patient survived but required pacemaker insertion and inotropic agents postoperatively. The 20 patients with prior coronary artery bypass grafting had a 50% mortality and 80% morbidity. Further, analysis by United Network for Organ Sharing functional status revealed a higher than expected mortality in all groups. The morbidity and mortality associated with liver transplantation is significantly increased in patients with coronary artery disease and is equally high in medically and surgically treated patients. By comparison, patients without coronary artery disease have a 3-year survival of 55.4% (status I) to 79.7% (status III and IV). The increased intraoperative and postoperative risk in patients with coronary artery disease undergoing liver transplantation should be considered when determining the candidacy of these patients as well as when providing informed consent.

Ionized hypomagnesemia in patients undergoing orthotopic liver transplantation: a complication of citrate intoxication.

Using a new ion-selective electrode, plasma concentration of ionized magnesium was measured in nine adult patients undergoing orthotopic liver transplantation. Baseline plasma ionized magnesium (IMg2+) concentration (0.49 +/- 0.07 mmol/L) was slightly below normal values (0.55-0.66 mmol/L, 95% CI): Six patients had ionized hypomagnesemia and two of these had total hypomagnesemia. Ionized IMg2+ concentration progressively decreased during the dissection (0.45 +/- 0.07 mmol/L, p < 0.05) and anhepatic stage (0.38 +/- 0.07 mmol/L, p < 0.05) and returned toward baseline values by 2 hours after graft reperfusion. Plasma ionized calcium levels and acid-base status were maintained within normal limits during surgery. Serum citrate concentration increased during the dissection (0.58 +/- 0.60 mmol/L) and anhepatic stages (1.18 +/- 0.78 mmol/L), the result of transfusion of citrate-rich blood products in the absence of adequate hepatic function, and gradually returned toward baseline values after graft reperfusion. IMg2+ concentration inversely correlated with the plasma citrate concentration (r2 = 0.54). The results of this study demonstrate that ionized hypomagnesemia invariably occurs during liver transplantation and suggest that this derangement may be a clinical concern, because magnesium is an important cofactor for the maintenance of cardiovascular homeostasis. The data further suggest the clinical importance of supplementation with magnesium based on the monitoring of plasma IMg2+ concentration.

Pharmacokinetics and pharmacodynamics of cisatracurium in patients with end-stage liver disease undergoing liver transplantation.

We determined the pharmacokinetics and pharmacodynamics of cisatracurium, one of the 10 isomers of atracurium, in 14 patients with end-stage liver disease undergoing liver transplantation and in 11 control patients with normal hepatic and renal function undergoing elective surgery. Blood samples were collected for 8 h after i.v. bolus administration of cisatracurium 0.1 mg kg-1 (2 x ED95). Plasma concentrations of cisatracurium and its metabolites were determined using an HPLC method with fluorescence detection. Pharmacokinetic variables were determined using non-compartmental methods. Neuromuscular block was assessed by measuring the electromyographic evoked response of the adductor pollicis muscle to train-of-four stimulation of the ulnar nerve using a Puritan-Bennett Datex (Helsinki, Finland) monitor. Pharmacodynamic modelling was completed using semi-parametric effect-compartment analysis. Volume of distribution at steady state was 195 (SD 38) ml kg-1 in liver transplant patients and 161 (23) ml kg-1 in control patients (P < 0.05), plasma clearance was 6.6 (1.1) ml kg-1 min-1 in liver transplant patients and 5.7 (0.8) ml kg-1 min-1 in control patients (P < 0.05), but elimination half-lives were similar: 24.4 (2.9) min in liver transplant patients vs 23.5 (3.5) min in control patients (ns). The time to maximum block was 2.4 (0.8) min in liver transplant patients compared with 3.3 (1.0) min in control patients (P < 0.05), but the clinical effective duration of action (time to 25% recovery) was similar: 53.5 (11.9) min in liver transplant patients compared with 46.9 (6.9) min in control patients (ns). The recovery index (25-75% recovery) was also similar in both groups: 15.4 (4.2) min in liver transplant patients and 12.8 (1.9) min in control patients (ns). After cisatracurium, peak laudanosine concentrations were 16 (5) and 21 (5) ng ml-1 in liver transplant and control patients, respectively. In summary, minor differences in the pharmacokinetics and pharmacodynamics of cisatracurium in liver transplant and control patients were not associated with any clinically significant differences in recovery profiles after a single dose of cisatracurium.

Living the dream. Shared governance in the role of nurse executive.

After one year of jointly assuming the responsibility for the Vice President's position of a 415-bed regional medical center, the directors of nursing analyzed the reality of living the dream. The authors discuss the personal issues of power and the joys and sorrows of group problem solving and decision making through shared governance, and present reactions from various levels of hospital personnel to this innovative and unconventional approach to nursing management.

Who's on first? Shared governance in the role of nurse executive.

After the resignation of their vice president for patient care services, five motivated directors of nursing accepted the challenge of launching an innovative and unconventional approach to nursing management. Using a shared governance framework and a medical staff model, they jointly assumed responsibility for the vice president position of a 415-bed regional medical center by rotating through the position annually.

Effect of nedocromil sodium and sodium cromoglycate against bronchoconstriction induced by inhaled adenosine 5'-monophosphate.

In this randomized, double-blind, placebo controlled study, the effect of prior inhalation of nebulized sodium cromoglycate (SCG) (7.3 +/- 0.6 mg) and nedocromil sodium (NED) (7.5 +/- 0.6 mg) was observed on adenosine 5'-monophosphate (AMP)-induced bronchoconstriction in 11 non-atopic asthmatic subjects. The geometric mean provocation doses of methacholine and AMP required to produce a 20% decrease in forced expiratory volume in one second (FEV1) (PD20FEV1) were 0.6 (0.1-18.8) and 5.1 (0.8-130.7) mumole respectively. The repeatability of the AMP challenge procedure for PD20FEV1 was within one doubling dose difference. SCG and NED, administered 30 min prior to bronchoprovocation with AMP, displaced the AMP dose-response curve to the right by 9.6 (1.5-41.6) (p less than 0.01) and 22.2 (3.7-89.1) (p less than 0.01)-fold, respectively, the difference between the two drugs being significant (p less than 0.05). There was a significant correlation (r = 0.7, p = 0.02) between the log dose ratios for PD20FEV1 for SCG and NED. We conclude that both SCG and NED protect against AMP-induced bronchoconstriction, NED being at least 2.3 (0.7-11.5)-fold more potent than SCG, and that they achieve this effect by a similar mechanism(s).