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Biomedical subjects

L Frenette

Publications and source records attributed to L Frenette.

At least 19 recordsLinked to original sources
PubMed2001

Combined cardiac surgery and liver transplantation.

During evaluation for liver transplantation, a 63-year-old man with cirrhosis secondary to hepatitis C was diagnosed with severe aortic stenosis (aortic valve area, 0.87 cm(2)) and coronary artery disease. A combined procedure involving aortic valve replacement (pericardial xenograft), coronary artery bypass surgery, and orthotopic liver transplantation was performed. Convalescence was uneventful, and at 2 years after the procedure, the patient has normal cardiac function, good prosthetic valve function, and biochemically normal liver function.

Aortic Valve↗
PubMed2000

The safety and efficacy of a two-dose daclizumab (zenapax) induction therapy in liver transplant recipients.

BACKGROUND: Induction therapy with daclizumab has been shown to be efficacious in the prevention of acute rejection in kidney transplant patients. The routine use of antibody induction therapy in liver transplantation has not gained widespread acceptance, except in the cases of renal insufficiency. The recent approval of daclizumab prompted us to initiate this pilot study using induction therapy in those patients at risk for developing posttransplant renal insufficiency. METHODS: This nonrandomized study examined the use of daclizumab in 39 of the last 97 liver transplants performed at the University of Alabama in Birmingham. The daclizumab group received 2 mg/kg intravenously before organ engraftment, and 38 of the 39 received 1 mg/kg intravenously on postoperative day 5. The control group consisted of the remaining 58 contemporary patients. Additional immunosuppression consisted of steroids, tacrolimus, or microemulsion cyclosporine in all patients and mycophenolate mofetil in selected patients. RESULTS: Pretransplant demographics were not significantly different between the groups. In the induction group there were significantly fewer males, 14 (36%) vs. 34 (59%) (P=0.03). They had greater renal insufficiency at the time of transplant, serum creatine 1.9+/-0.37 mg/dl vs. 0.8+/-0.5; P=0.0009, and more patients were at higher acuity (status 1 and 2A): 12 (31%) vs. 3 (5%) P=0.0006 than in the noninduction group. By postoperative day 7, renal function improved in the induction group such that it was not significantly different from the noninduction group and remained similar throughout the rest of the follow-up. The induction group also experienced significantly less acute rejection, 7 (18%) vs. 23 (40%) (P=0.02) than in the noninduction group in the first 6 months. The 1-, 3-, and 6-month patient survival rates were similar in the induction group, 97.4%, 97.4%, and 97.4%, vs. non-induction 94.8%, 93.0%, and 93% (P=NS). The incidence of cytomegalovirus, in the first 6 months, in the induction group was four (10%) vs. five (9%) (P=NS) in the noninduction group. CONCLUSION: In the pilot study, induction therapy with daclizumab was safe, facilitated improvement in renal function, and appeared to reduce the incidence of acute rejection. Combination therapy with daclizumab may be an important adjunct in immunosuppressive strategies for liver transplant recipients.

Adult↗
PubMed1999

Tolerability and side effects of anti-CD3-immunotoxin in preclinical testing in kidney and pancreatic islet transplant recipients.

INTRODUCTION: Anti-CD3-immunotoxin (alpha-CD3-IT) promotes allograft tolerance in nonhuman primates owing to efficient depletion of sessile and circulating T cells. Common side effects of vascular leak syndrome, hepatotoxicity, and nephrotoxicity have limited tolerability of other immunotoxins. We report on preclinical studies of alpha-CD3-IT-related side effects. METHODS: Normal rhesus monkeys received a kidney transplant and alpha-CD3-IT alone (on day -to +2) or in combination with brief peritransplant adjunctive immunosuppressive therapy. Some received donor CD34+ cells. Blood chemistries, complete blood count, weight, liver, and kidney biopsies were examined for immunotoxin-related changes. Five spontaneously diabetic primates also received alpha-CD3-IT, three of whom had a pancreas islet transplant. RESULTS: The main side effect of alpha-CD3-IT, vascular leak syndrome, was entirely prevented by adjunctive immunosuppressive therapy. Renal and liver function tests and biopsies revealed a lack of nephrotoxicity and hepatotoxicity. All had transient weight loss (14+/-5%). Without infusion of donor CD34+ cells, 97% had full weight recovery. Of those given donor CD34+ cells, 50% were euthanized for wasting. CONCLUSIONS: Side effects of alpha-CD3-IT are manageable and should not prevent therapeutic application.

Animals↗
PubMed1999

The acute pain service.

The often inadequate treatment of acute pain is more often due to improper application of available therapies than to the unavailability of effective drugs and techniques. In our institution, the establishment of an acute pain service has improved the safety and efficacy of postoperative pain control. This has been achieved not simply through the immediate availability of a group of specialist physicians and nurses, but also through staff education. The latter has addressed many of the misconceptions preventing proper and safe use of potent analgesic agents. Although provision of intravenously administered patient-controlled analgesia appears not to influence patient outcome, it can result in improved analgesia and patient satisfaction when used properly. Epidurally administered patient-controlled analgesia, on the other hand, appears to provide superior relief of activity pain and earlier resolution of postoperative ileus. The administration of local anesthetic agents, in particular, may reduce reflex diaphragmatic dysfunction following thoracoabdominal surgery and decrease the incidence of graft occlusion following lower extremity vascular procedures. Epidural catheter placement, however, is not without risk, especially in subjects with an established or potential coagulopathy.

Analgesia↗
PubMed1998

Peritransplant tolerance induction with anti-CD3-immunotoxin: a matter of proinflammatory cytokine control.

BACKGROUND: Tolerance is gaining momentum as an approach to reduce lifelong immunosuppressive therapy while improving transplant longevity. Anti-CD3 immunotoxin (IT), FN18-CRM9, has potential to induce tolerance owing to its exceptional ability to deplete sessile lymph node T cells. However, if initiated at the time of transplantation, alpha-CD3-IT alone elicits a proinflammatory cytokine response, precluding establishment of tolerance. METHODS: Four groups of rhesus monkeys received kidney allografts and immunosuppression. Three groups received alpha-CD3-IT alone or alpha-CD3-IT supplemented with 15-deoxyspergualin (DSG) and/or methylprednisolone (MP). One group received alpha-CD3-monoclonal antibody with DSG and MP. Cytokines were measured by enzyme-linked immunosorbent assay. RESULTS: Supplementing peritransplant alpha-CD3-IT treatment with a brief course of DSG and MP promoted rejection-free kidney allograft acceptance in 75% of macaques followed for up to 550 days. Among those given alpha-CD3-IT alone or with MP, none were long-term survivors. Tolerance developed after alpha-CD3-IT, DSG, and MP treatment, but not when the unconjugated a-CD3 monoclonal antibody was substituted for IT. Systemic production of proinflammatory cytokines interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha induced after peritransplant alpha-CD3-IT was prevented only in animals given DSG. Despite high levels of interleukin (IL)-12 in the first month after transplant, tolerant recipients exhibited IL-12 resistance, as evidenced by baseline plasma levels of IFN-gamma but elevated IL-4. DSG was shown to inhibit IL-12-driven IFN-gamma production by a mechanism associated with inhibition of nuclear factor kappa-B. CONCLUSIONS: In this model, peritransplant induction of tolerance is promoted by efficient elimination of sessile lymph node T cells and control of the proinflammatory IFN-gamma response by a mechanism that appears to involve resistance to IL-12.

Animals↗
PubMed1998

Conjugated estrogen reduces transfusion and coagulation factor requirements in orthotopic liver transplantation.

UNLABELLED: We conducted a prospective, randomized study to determine the efficacy of conjugated estrogen in reducing blood product transfusion during orthotopic liver transplantation (OLT). Patients undergoing OLT were included in the study. Only those having a reaction time of more than 30 mm or 15 min (19 -28 mm) on computed thromboelastography (CTEG) at the beginning of surgery were enrolled in the study. Patients were randomized to receive either conjugated estrogen (CE) or placebo. Every patient received a first dose of CE (100 mg i.v.) (20 mL) or placebo (20 mL of isotonic sodium chloride solution) at the beginning of the procedure and a second dose of CE (100 mg i.v.) or 20 mL of placebo (20 mL of isotonic sodium chloride solution) just after reperfusion of the new graft. The two groups were similar in age, weight, requirement for veno-veno bypass, time on veno-veno bypass, CTEG measurement, and preoperative hemoglobin and platelet values. Blood products were given in relation to hematocrit and coagulation (CTEG) variables, which were measured every hour during the surgery. The amount of transfused blood products did not differ in terms of units of cryoprecipitate, but the intraoperative requirements for red blood cells (6 +/- 3 vs 9 +/- 6 U; P = 0.05), platelets (12 +/- 8 U vs 18 +/- 10 U; P = 0.05) and fresh-frozen plasma (3 +/- 3 U vs 6 +/- 4 U; P = 0.001) was significantly less in the estrogen group than in the control group. We conclude that CE is associated with a significant decrease in use of fresh-frozen plasma, platelets, and red blood cells during OLT. IMPLICATIONS: In this study, we prospectively investigated whether i.v. conjugated estrogen could decrease blood product transfusion during orthotopic liver transplantation. Conjugated estrogen-treated patients received less fresh-frozen plasma, red blood cells, and platelets. In this population of patients, conjugated estrogen can be a useful addition in coagulation management during orthotopic liver transplantation.

Blood Coagulation Factors↗
PubMed1998

Effectiveness of conjugated estrogen in orthotopic liver transplantation.

BACKGROUND: A retrospective study was conducted at a university hospital to determine the efficacy of conjugated estrogen in reducing blood product transfusion during orthotopic liver transplantation. METHODS: The charts of patients who had orthotopic liver transplantation were retrospectively reviewed. Only those having a reaction time > 30 mm or 15 minutes (normal = 19 mm to 28 mm) on computerized thromboelastogram (CTEG) at the beginning of surgery were included. One group of patients received a first dose of conjugated estrogen (100 mg i.v.) at the beginning of the case and a second dose (100 mg i.v.) just after reperfusion of the new graft. The control group did not receive estrogen. The two groups were similar in age, weight, first TEG measurements, final intraoperative hemoglobin concentration and platelet count. Blood products were given in response to hematocrit and CTEG measurements, which were determined every hour during surgery. RESULTS: The two groups did not differ in units of cryoprecipitate and platelets administered, but the intraoperative requirements for red blood cells and fresh frozen plasma were significantly lower in the estrogen group than in the control group. CONCLUSIONS: Administration of conjugated estrogen is associated with a statistically significant decrease in use of red blood cells and fresh frozen plasma during orthotopic liver transplantation.

Adult↗
PubMed1996

A comparison of alfentanil, esmolol, lidocaine, and thiopental sodium on the hemodynamic response to insertion of headrest skull pins.

STUDY OBJECTIVES: To compare the effects of four techniques for preventing or blunting the hypertensive response to the insertion of Mayfield headrest skull pins: intravenous (IV) alfentanil (ALF), esmolol (ESM), thiopental sodium (TPL), and local anesthesia using plain lidocaine (Xylocaine; XYL). DESIGN: Randomized open study. PATIENTS: 40 adult patients undergoing intracranial or spinal surgery requiring the use of Mayfield headrest skull pins for head positioning and immobilization. INTERVENTIONS: 20 minutes after anesthetic induction, and 2 to 3 minutes prior to the insertion of headrest skull pins, one of three drugs was administered IV: ALF 10 mcg/kg, ESM 1 mg/kg, or TPL 1.5 mg/kg. The fourth drug, XYL, was administered by injection into the scalp. MEASUREMENTS AND MAIN RESULTS: Blood pressure and heart rate (HR) were recorded immediately prior to and after pin insertion with balanced general anesthesia, and at 30, 60, 120, and 180-second intervals after pin insertion. The measurements were compared with the immediate preinsertion values. In the ALF and XYL groups, there was no significant increase in mean arterial pressure (MAP) or HR for any of the measurement periods. MAP was elevated immediately on pin insertion and for up to 2 minutes in the TPL group, and for up to 3 minutes in the ESM group (p < 0.05). HR changes were seen in the TPL group for up to one minute (p < 0.05). Increases in systolic blood pressure were seen in the TPL and ESM groups for up to 3 minutes, and in diastolic blood pressure for up to 2 minutes (p < 0.05). No other significant changes were observed. CONCLUSIONS: IV ALF and local injection of XYL in the scalp prevent the hemodynamic response to the insertion of skull pins in anesthetized patients. Neither ESM nor TPL prevented the hypertensive response. Local anesthetic injection into the scalp requires coordination between the anesthesiologist and surgeon, it carries the risk of needle stick injury, and it must be repeated if the surgeon repositions the headrest. The rapid onset and short half-life of ALF, coupled with the absence of hemodynamic effects at the dose used, makes this drug an alternative to the use of XYL injection.

Adrenergic beta-Antagonists↗
PubMed1995

Intraoperative transesophageal echocardiography in orthotopic liver transplantation in a patient with hypertrophic cardiomyopathy.

With improvements in the surgical technique for orthotopic liver transplantation, patients with significant underlying systemic disease are considered candidates for transplantation, thus increasing the complexity of the medical management of these patients and necessitating additional monitoring in order to minimize the anesthetic risk. We describe the anesthetic management of orthotopic liver transplantation for a patient with severe hypertrophic cardiomyopathy and mitral insufficiency. In this case, transesophageal echocardiography proved useful in the management of the postreperfusion period of the surgical procedure.

Anesthesia↗
PubMed1995

The effect of acute hypocapnia on middle cerebral artery transcranial Doppler velocity during orthotopic liver transplantation: changes at reperfusion.

This study examines the effects of acute hypocapnia, instituted prior to reperfusion of the graft liver, on the middle cerebral artery (MCA) Doppler blood flow velocity response to reperfusion during orthotopic liver transplantation in humans. Seventeen patients with chronic liver disease underwent continuous, noninvasive Doppler imaging of the MCA. Hyperventilation to an end-tidal Pco2 of 25 +/- 1 mm Hg was associated with a decrease in mean MCA flow velocity (FVm) from 51.6 +/- 5.7 to 37.0 +/- 3.3 cm/s (P < 0.05). After reperfusion, the Paco2 increased from 32 +/- 1 to 40 +/- 1 mm Hg (P < 0.05), mean arterial pressure (MAP) decreased from 76 +/- 3 to 60 +/- 2 mm Hg, and the FVm increased from 37.0 +/- 3.3 to 54.0 +/- 4.7 cm/s (P < 0.05). FVm increased postreperfusion despite prior hyperventilation, decreased MAP, and abrupt increases in central venous and pulmonary artery pressure, but FVm did not exceed the prereperfusion level. In 10 of the 17 patients, the baseline FVm versus Paco2 response slopes and Paco2 measured postreperfusion were used to predict the FVm response to Paco2 after reperfusion. The slopes were similar to those reported for anesthetized patients without liver disease. Predicted FVm exceeded measured FVm in 9 of the 10 patients. We conclude that mild hyperventilation prior to reperfusion of the graft liver prevents FVm increases above prereperfusion baseline level.

Acute Disease↗
PubMed1994

Gastric intramural pH as indicator of early allograft viability in orthotopic liver transplantation.

The determination of the viability of OLT grafts has relied upon metabolic tests of the liver, which take several hours to evaluate and therefore are only conclusive in most patients well into the postoperative period. Earlier diagnosis of graft failure or nonfunction would allow intraoperative reassessment of surgical technique and, in the case of graft failure, earlier planning for retransplantation. Since gastrointestinal mucosal ischemia is one of the earliest manifestations of impaired core tissue in the critically ill, a tonometric nasogastric tube (Tonomitor) was used in our patients to measure intramucosal gastric pH (pHi) during the preanhepatic (stage I), anhepatic (stage II), and neohepatic (stage III) phases of OLT in 35 patients as an indicator of graft liver function and viability. Based on the results of the pHi measurement 30 min after reperfusion during stage III, patients were divided into 2 groups using a pHi of 7.30 as the dividing point. Patients with a pHi equal or higher than 7.30 were assigned to group 1 (n = 24) and patients with a pHi lower than 7.30 were assigned to group 2 (n = 11). The pHi in group 1 patients averaged 7.37 +/- 0.5 30 min after reperfusion and throughout surgery. The pHi in group 2 patients was lower than that of the group 1 patients 30 min after reperfusion, 7.23 +/- 0.04 (P < 0.001). The pHi in 10 group 2 patients returned to normal within 3 hr after reperfusion and the pHi values for these patients were not significantly different from those of group 1 at 3 hr after reperfusion. The pHi in 1 group 2 patient remained lower than 7.30 and never returned to normal; this patient underwent retransplantation the following day. Utilizing the tonometric nasogastric tube to sample intramucosal pH allowed early detection of graft function and intermittent trending of pHi in patients with questionable graft function during the operative period. It also provided a means of assessing graft function independent of enzymatic criteria, which provide little information in the early phase of transplantation.

Adult↗
PubMed1994

[Vaccination in Togo].

The author describes her participation in an immunization project in Togo, one of many such projects supported by Canada's International Immunization Program. The Togo project was run by CUSO in partnership with the Canadian Public Health Association. In Togo, the infant mortality rate is significant. Thus the institution of an immunization program against major childhood illness (diphtheria, polio, tetanus, pertussis, measles and tuberculosis) was of paramount importance. Based in the maritime region of Togo, the project the author worked on helped 60,000 children and 200,000 women of childbearing age. The health team didn't attempt to change the behavior of the people of Togo since their cultural health care beliefs have existed for centuries and differ significantly from those of North Americans. Rather, efforts centered on health teaching, which increased the immunization rate from 16 to 63 per cent and decreased the incidence of disease.

Humans↗
PubMed1993

Insulin decreases the serum potassium concentration during the anhepatic stage of liver transplantation.

BACKGROUND: Severe hyperkalemia is a serious problem during orthotopic liver transplantation. The effectiveness of insulin in decreasing serum potassium concentration during the anhepatic stage of orthotopic liver transplantation was investigated. METHODS: Forty patients with serum potassium concentrations greater than 4.0 mM/L at the onset of the anhepatic stage were randomized into two groups. Control group patients (n = 20) received no treatment, and treatment group patients (n = 20) received an intravenous bolus of regular insulin (20 u) 10 min into the anhepatic stage, followed by a glucose infusion (500 ml 5% dextrose in water) over 15 min. RESULTS: In the control group, the potassium concentration did not change, whereas in the treatment group, it decreased from 4.70 +/- 0.54 to 4.18 +/- 0.63 mM/L (mean +/- SD) within 15 min and to 3.57 +/- 0.55 mM/L 60 min after therapy. The potassium concentration was less in the treatment group than in the control group within 30 min of treatment (3.97 +/- 0.52 vs. 4.49 +/- 0.43 mM/L, respectively; P < 0.05). The potassium concentration increased similarly 30 s after graft reperfusion in both groups of patients, but was less in the treatment group (5.91 +/- 1.63 vs. 7.37 +/- 1.67 mM/L, respectively; P < 0.05). The potassium concentration returned to prereperfusion levels within 5 min after graft reperfusion. CONCLUSIONS: In patients undergoing orthotopic liver transplantation, the administration of insulin rapidly decreases serum potassium concentration, even in the absence of the liver, suggesting an important contribution by extrahepatic tissues in the insulin-stimulated uptake of potassium.

Adult↗
PubMed1991

Interpleural analgesia improves pulmonary function after cholecystectomy.

The purpose of this study was to examine the effects of interpleural bupivacaine on analgesia and ventilatory capacity after cholecystectomy. Forty-two patients undergoing elective cholecystectomy were randomly assigned to two groups: one to receive interpleural administration of bupivacaine-adrenaline mixture (Group 1 = 22 patients) and the other standard administration of intramuscular meperidine (Group 2 = 20 patients) for postoperative pain relief. The intensity of pain was evaluated by a visual analogue scale (VAS) preoperatively as well as at 2, 8, 24 and 48 hr postoperatively. At the same time, FVC and FEV1.0 measurements were obtained for all patients. The group given interpleural bupivacaine had better pain relief with mean VAS of 0.6 +/- 0.9 (mean +/- SD) 1.1 +/- 1.4, 0.6 +/- 0.9 and 0.8 +/- 1.2 compared with 5.2 +/- 2.2, 5.8 +/- 2.7, 5.5 +/- 2.2 and 4.5 +/- 1.8 for patients receiving meperidine (P less than 0.001). The patients in Group 1 also had larger FVC and FEV than those in Group 2: FVC 22 +/- 14.5 per cent vs 32 +/- 15.2 per cent (P less than 0.005), FEV1.0 25 +/- 15.5 vs 38 +/- 14.8 per cent (P less than 0.001) (mean +/- SD). We conclude that the interpleural analgesia can achieve better pain relief with greater ventilatory capacity than a standard analgesic regimen in the first two days after cholecystectomy.

Analgesia↗