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Biomedical subjects

D Amar

Publications and source records attributed to D Amar.

At least 19 recordsLinked to original sources
PubMed2006

Conditional and specific NF-kappaB blockade protects pancreatic beta cells from diabetogenic agents.

Type 1 diabetes is characterized by the infiltration of inflammatory cells into pancreatic islets of Langerhans, followed by the selective and progressive destruction of insulin-secreting beta cells. Islet-infiltrating leukocytes secrete cytokines such as IL-1beta and IFN-gamma, which contribute to beta cell death. In vitro evidence suggests that cytokine-induced activation of the transcription factor NF-kappaB is an important component of the signal triggering beta cell apoptosis. To study the in vivo role of NF-kappaB in beta cell death, we generated a transgenic mouse line expressing a degradation-resistant NF-kappaB protein inhibitor (DeltaNIkappaBalpha), acting specifically in beta cells, in an inducible and reversible manner, by using the tet-on regulation system. In vitro, islets expressing the DeltaNIkappaBalpha protein were resistant to the deleterious effects of IL-1beta and IFN-gamma, as assessed by reduced NO production and beta-cell apoptosis. This effect was even more striking in vivo, where nearly complete protection against multiple low-dose streptozocin-induced diabetes was observed, with reduced intraislet lymphocytic infiltration. Our results show in vivo that beta cell-specific activation of NF-kappaB is a key event in the progressive loss of beta cells in diabetes. Inhibition of this process could be a potential effective strategy for beta-cell protection.

Active Transport, Cell Nucleus↗
PubMed2001

Correlation of peripheral venous pressure and central venous pressure in surgical patients.

OBJECTIVE: To determine the degree of agreement between central venous pressure (CVP) and peripheral venous pressure (PVP) in surgical patients. DESIGN: Prospective study. SETTING: University hospital. PARTICIPANTS: Patients without cardiac dysfunction undergoing major elective noncardiac surgery (n = 150). MEASUREMENTS AND MAIN RESULTS: Simultaneous CVP and PVP measurements were obtained at random points in mechanically ventilated patients during surgery (n = 100) and in spontaneously ventilating patients in the postanesthesia care unit (n = 50). In a subset of 10 intraoperative patients, measurements were made before and after a 2-L fluid challenge. During surgery, PVP correlated highly to CVP (r = 0.86), and the bias (mean difference between CVP and PVP) was -1.6 +/- 1.7 mmHg (mean +/- SD). In the postanesthesia care unit, PVP also correlated highly to CVP (r = 0.88), and the bias was -2.2 +/- 1.9 (mean +/- SD). When adjusted by the average bias of -2, PVP predicted the observed CVP to within +/-3 mmHg in both populations of patients with 95% probability. In patients receiving a fluid challenge, PVP and CVP increased similarly from 6 +/- 2 to 11 +/- 2 mmHg and 4 +/- 2 to 9 +/- 2 mmHg. CONCLUSION: Under the conditions of this study, PVP showed a consistent and high degree of agreement with CVP in the perioperative period in patients without significant cardiac dysfunction. PVP -2 was useful in predicting CVP over common clinical ranges of CVP. PVP is a rapid noninvasive tool to estimate volume status in surgical patients.

Aged↗
PubMed2001

Diltiazem treatment does not alter renal function after thoracic surgery.

BACKGROUND: There are conflicting reports on the effects of diltiazem treatment on renal function in surgical patients. We sought to determine whether diltiazem treatment alters renal function in patients undergoing major thoracic surgery. METHODS: In a prospective study, 330 patients scheduled for elective thoracic surgery received either IV diltiazem (n = 167) or placebo (n = 163) immediately after the operation and orally thereafter for 14 days in an effort to prevent postoperative atrial arrhythmias. Serum creatinine and BUN levels were compared before and during the first postoperative week. RESULTS: Patients treated with diltiazem were similar to control subjects in terms of age (mean +/-SD, 66 +/- 10 years vs 67 +/- 10 years, respectively), baseline serum creatinine or BUN levels, prevalence of comorbid conditions, and surgical characteristics. During the first 5 postoperative days, the two groups did not differ in terms of serum creatinine or BUN levels. The incidence of renal failure was 0.6% in the diltiazem group and 1.2% in the placebo group (difference was not significant). There was no difference in the length of hospitalization or mortality rate. CONCLUSIONS: In patients without renal disease who are undergoing elective thoracic surgery, prophylactic diltiazem treatment did not alter postoperative renal function.

Aged↗
PubMed2000

Perioperative alterations in plasma endothelin-1 and echocardiographic correlates of right heart function.

OBJECTIVE: To determine whether greater changes in plasma endothelin-1 (ET-1) concentrations and right ventricular systolic pressure occur after major thoracic surgery than after major abdominal operations. DESIGN: Prospective study. SETTING: University hospital. PARTICIPANTS: Patients undergoing elective thoracotomies (n = 12) or laparotomies (n = 10). INTERVENTIONS: ET-1 was measured from blood obtained before anesthesia and again on postoperative days 1, 2, 3, and 5 (or 6). Transthoracic echocardiography was performed before surgery and on postoperative day 2 to evaluate right-sided heart function. MEASUREMENTS AND MAIN RESULTS: After abdominal and thoracic surgery, systemic and estimated pulmonary vascular pressures were normal in both groups and unaffected by surgery. Plasma ET-1 concentrations decreased from baseline values during the first postoperative week with no differences between the groups. CONCLUSIONS: In patients without organic heart disease, plasma ET-1 levels do not increase in response to major abdominal or thoracic surgery. Whether or not plasma ET-1 concentrations are elevated in patients developing clinically significant postoperative pulmonary hypertension requires further study.

Aged↗
PubMed2000

Effects of diltiazem prophylaxis on the incidence and clinical outcome of atrial arrhythmias after thoracic surgery.

OBJECTIVES: We sought to determine whether early prophylaxis with an L -type calcium channel blocker reduces the incidence and morbidity associated with atrial fibrillation/flutter and supraventricular tachyarrhythmia after major thoracic operations. METHODS: In this randomized, double-blind, placebo-controlled study, 330 patients were given either intravenous diltiazem (n = 167) or placebo (n = 163) immediately after lobectomy (> or =60 years) or pneumonectomy (> or =18 years) and orally thereafter for 14 days. The primary end point with respect to efficacy was a sustained (> or =15 minutes) or clinically significant atrial arrhythmia during treatment. RESULTS: Postoperative atrial arrhythmias (atrial fibrillation/flutter = 60; supraventricular tachyarrhythmias = 5) occurred in 25 (15%) of the 167 patients in the diltiazem group and 40 (25%) of the 163 patients in the placebo group (P = .03). When compared with placebo, diltiazem nearly halved the incidence of clinically significant arrhythmias (17/167 [10%] vs. 31/163 [19%], P = .02). The 2 groups did not differ in the incidence of other major postoperative complications or overall duration or costs of hospitalization. No serious adverse effects caused by diltiazem were seen. CONCLUSIONS: After major thoracic operations, prophylactic diltiazem reduced the incidence of clinically significant atrial arrhythmias in patients considered at high risk for this complication.

Administration, Oral↗
PubMed1999

Signal-averaged P-wave duration does not predict atrial fibrillation after thoracic surgery.

BACKGROUND: Atrial fibrillation (AF) is the most common dysrhythmia seen early after major thoracic surgery but occurs infrequently after minor thoracic or other operations. A prolonged signal-averaged P-wave duration (SAPWD) has been shown to be an independent predictor of AF after cardiac surgery. The authors sought to determine whether a prolonged SAPWD alone or in combination with clinical or echocardiographic correlates predicts AF after elective noncardiac thoracic surgery. METHODS: Of the 250 patients enrolled, 228 were included in the final analysis. Preoperative SAPWD was obtained in 155 patients who had major thoracic surgery and in 73 patients undergoing minor thoracic or other operations who served as comparison control subjects. The SAPWD was recorded from three orthogonal leads using a sinus P-wave template. The filtered vector composite was used to measure total P-wave duration. Clinical, surgical, and echocardiographic parameters were collected and patients followed for 30 days after surgery for the development of symptomatic AF. RESULTS: Symptomatic AF developed in 18 of 155 (12%) patients undergoing major thoracic surgery and in 1 of 73 (1%) patients having minor thoracic or abdominal surgery, most commonly 2 or 3 days after surgery. In comparison with similar patients undergoing major thoracic surgery without AF, those who developed AF were older (66+/-8 vs. 62+/-10 yr; P = 0.04) but did not differ in SAPWD (145+/-17 vs. 147+/-16, ms) in standard electrocardiographic P-wave duration (105+/-7 vs. 107+/-10 mns), incidence of left-ventricular hypertrophy on 12-lead electrocardiography, male sex, history of hypertension, diabetes, or coronary heart disease. Thoracic-surgery patients at risk for postoperative AF did not differ from all other patients at low risk for AF in clinical or SAPWD parameters. CONCLUSIONS: Under the conditions of this study, SAPWD did not differentiate patients who did or did not develop AF after noncardiac thoracic surgery, and therefore its measurement cannot be recommended for the routine evaluation of these patients. Older age continues to be a risk factor for AF after thoracic surgery.

Adult↗
PubMed1998

Persistent alterations of the autonomic nervous system after noncardiac surgery.

UNLABELLED: BACKGROUND. Changes in the sympathetic nervous system may be a cause of postoperative cardiovascular complications. The authors hypothesized that changes in both beta-adrenergic receptor (betaAR) function (as assessed in lymphocytes) and in sympathetic activity (assessed by plasma catecholamines and by heart rate variability [HRV] measurements obtained from Holter recordings) occur after operation. METHODS: The HRV parameters were measured in 28 patients having thoracotomy (n = 14) or laparotomy (n = 14) before and for as long as 6 days after operation. Transthoracic echocardiography was performed before and on postoperative day 2. Lymphocytes were also isolated from blood obtained before anesthesia and again on postoperative days 1, 2, 3, and 5 (or 6). They were used to examine betaAR number (Bmax) and cyclic adenosine monophosphate (cAMP) production after stimulation with isoproterenol and prostaglandin E1. In addition, plasma epinephrine, norepinephrine, and cortisol concentrations were determined at similar intervals. RESULTS: After abdominal and thoracic surgery, most time and all frequency indices of HRV decreased significantly, as did Bmax and basal and isoproterenol-stimulated cAMP production. The decrements in HRV correlated with those of Bmax and isoproterenol-stimulated cAMP throughout the first postoperative week and inversely correlated with the increase in heart rate. Plasma catecholamine concentrations did not change significantly from baseline values, but plasma cortisol levels did increase after operation in both groups. Left ventricular ejection fraction was normal in both groups and unaffected by surgery. CONCLUSIONS: Persistent downregulation and desensitization of the lymphocyte betaAR/adenylyl cyclase system correlated with decrements in time and frequency domain indices of HRV throughout the first week after major abdominal or thoracic surgery. These physiologic alterations suggest the continued presence of adaptive autonomic regulatory mechanisms and may explain why the at-risk period after major surgery appears to be about 1 week or more.

Aged↗
PubMed1998

Bupivacaine 0.01% and/or epinephrine 0.5 microg/ml improve epidural fentanyl analgesia after cesarean section.

BACKGROUND: The authors studied the addition of bupivacaine and epinephrine, separately and together, to epidural fentanyl to determine whether this improved postcesarean analgesia and reduced the incidence of side effects. METHODS: After elective cesarean section, 100 parturient patients who received fentanyl (3 microg/ml) epidurally for 48 h were allocated randomly in a double-blinded manner to four groups to receive, in addition to the study solution, 0.01% bupivacaine, 0.5 microg/ml epinephrine, both, or neither. A neurologic assessment of breast-fed neonates was made at 2 and 48 h of life. Plasma fentanyl concentrations were determined in a subset of patients at intervals after treatment. RESULTS: Patients receiving fentanyl alone made more attempts at patient-controlled analgesia (P < 0.01), required a greater total dose of fentanyl (P < 0.01), reported more pain (P < 0.003) and less satisfaction (P < 0.003), and had more nausea and urinary retention (P < 0.05) than all other groups. Patients who received bupivacaine with or without epinephrine had better overall satisfaction scores than those who did not receive bupivacaine (P < 0.001), and they required less fentanyl (P < 0.02) than patients who received fentanyl with only epinephrine. Motor blockade or orthostatic hypotension did not develop in any patient, and all patients could ambulate without difficulty. Neurobehavioral scores, which were similar among all neonates, were within the normal range. Plasma concentrations of fentanyl increased after epinephrine-containing solutions were discontinued. CONCLUSIONS: During the conditions of this study, the addition of epinephrine and bupivacaine to a 3-microg/ml epidural fentanyl solution for postcesarean section pain relief provided superior analgesia compared with fentanyl alone or fentanyl with epinephrine. Whether increasing the concentration of fentanyl alone might improve the efficacy of fentanyl remains unclear.

Adult↗
PubMed1998

Cardiac arrhythmias.

Supraventricular dysrhythmias (SVDs) present the most frequent medical complication after thoracic surgery and have been associated with prolonged hospital stays. The reported incidence of SVDs in the thoracic surgery patient population ranges from 10% to 40%, with factors such as age and extent of surgery markedly influencing the incidence. This article focuses on new issues leading to improved understanding of the pathophysiology and mechanisms of SVDs after surgery. New approaches directed at prophylaxis and acute therapy of SVDs are discussed, as are recommendations to prevent thromboembolic events due to atrial dysrhythmias following thoracic surgery.

Age Factors↗
PubMed1997

Epidural block for obstetrics: comparison of bolus injection of local anesthetic with gravity flow technique.

STUDY OBJECTIVE: To test the hypothesis that slow administration of local anesthetic into the epidural space by gravity flow reduces the incidence of signs and symptoms of unintended injection. DESIGN: Prospective, randomized study. SETTING: Teaching hospital. PATIENTS: 600 ASA physical status l and II parturients scheduled for labor and delivery or elective cesarean section. INTERVENTIONS: After identification of the epidural space with pulsations of an air-fluid column, parturients for vaginal delivery (n = 380) were randomized to receive a test dose of 3 ml 3% 2-chloroprocaine with epinephrine 20 micrograms, two doses of 7 ml bupivacaine 0.03% with sufentanil 1 microgram/ml and epinephrine 2 micrograms/ml by either gravity flow (Group 1) given over 30 seconds or by bolus injection (Group 2) given over 5 seconds through the epidural needle; parturients for Cesarean delivery (n = 220) were randomized to receive a test dose and two doses of 6 ml lidocaine 2% with sufentanil 1 microgram/ml and epinephrine 2 micrograms/ml by either gravity flow or by bolus injection through the epidural needle. Changes in maternal heart rate (HR) and blood pressure, signs of intravascular injection, and adverse effects of epidural bupivacaine-sufentanil were recorded after each dose. MEASUREMENTS AND MAIN RESULTS: Gravity flow administration (Group 1) was associated with a smaller increase in mean maternal HR (p < 0.001), less hypotension (p < 0.01), sedation (p < 0.01), nausea (p = 0.01), and segmental spread (p < 0.0001) than were corresponding doses given by traditional bolus injection (Group 1) for vaginal or Cesarean deliveries. The incidence of systemic toxicity was zero of 300 (0%) with gravity flow and 4 of 300 (1.3%) by bolus injection, p = 0.12, Fisher's exact test. No patient in either group had an accidental intrathecal injection. CONCLUSION: Gravity flow administration of local anesthetic-opioid solution during epidural block for obstetrics was associated with fewer signs of systemic drug absorption and cardiovascular perturbations than was the traditional bolus injection. This study supports the current opinion that slow administration of local anesthetic during epidural block contributes to fewer adverse events.

Anesthesia, Epidural↗
PubMed1997

Effects of diltiazem versus digoxin on dysrhythmias and cardiac function after pneumonectomy.

BACKGROUND: This prospective study was designed to determine whether diltiazem is superior to digoxin for the prophylaxis of supraventricular dysrhythmias (SVD) after pneumonectomy or extrapleural pneumonectomy (EPP) and to assess the influence of these drugs on perioperative cardiac function. METHODS: Seventy consecutive patients without previous SVD were randomly allocated immediately after pneumonectomy or EPP to receive diltiazem (n = 35) or digoxin (n = 35). Diltiazem-treated patients received a slow intravenous loading dose of 20 mg, followed by 10 mg intravenously every 4 hours for 24 to 36 hours, then 180 to 240 mg orally daily for 1 month. Digoxin-treated patients received a 1-mg intravenous loading in the first 24 to 36 hours, then 0.125 to 0.25 mg orally daily for 1 month. A concurrent prospective cohort of 40 patients without previous SVD, who did not participate in the study and underwent pneumonectomy or EPP without prophylaxis, served as a comparison group for SVD occurrence. Serial Doppler echocardiograms were performed to assess cardiac function and all patients were continuously monitored with Holter recorders for 3 days. Data were analyzed by intent-to-treat. RESULTS: In patients undergoing standard or intrapericardial pneumonectomy, diltiazem prevented the overall incidence of postoperative SVD when compared with digoxin, 0 of 21 patients versus 8 of 25 patients, respectively, p < 0.005. When EPP patients were included in the analysis, diltiazem decreased the incidence of all SVD from 11 of 35 patients (31%) to 5 of 35 patients (14%) when compared with digoxin, p = 0.09. Digoxin-treated patients had a similar incidence of all SVD (31%) as concurrent controls (11 of 40 patients [28%]). The two treated groups did not differ in right or left atrial size, left ventricular ejection fraction, or right heart pressure. When all patients were combined, those in whom SVD developed were significantly older (65 +/- 12 years versus 55 +/- 11 years, p = 0.004) and had a longer median hospital stay (9 versus 6 days, p = 0.03), when compared with those in whom SVD did not develop, respectively. The subset of patients undergoing EPP had a greater incidence of atrial fibrillation and electrocardiographic changes suggestive of postoperative pericarditis than all other pneumonectomy patients. CONCLUSIONS: Diltiazem was both safe and more effective than digoxin in reducing the overall incidence of SVD after standard or intrapericardial pneumonectomy. Digoxin therapy had no effect on the incidence of postoperative SVD and is not recommended for prophylaxis of SVD. Dysrhythmias after pneumonectomy or EPP occur in older patients and are associated with a greater length of hospital stay.

Aged↗
PubMed1997

Cardiopulmonary complications of esophageal surgery.

This article reviews preoperative cardiopulmonary concerns that may need medical investigation prior to surgery. Common intraoperative hemodynamic disturbances and possible causes of respiratory failure are discussed. The cardiopulmonary complications occurring after esophagectomy reported in large series are presented.

Atrial Fibrillation↗
PubMed1997

Prevention and management of dysrhythmias following thoracic surgery.

Supraventricular dysrhythmias (SVDs) occur frequently after thoracic surgery and have been associated with prolonged hospital stays. The reported incidence of supraventricular dysrhythmias in the thoracic surgery patient population ranges from 10% to 40%, with factors such as age and extent of surgery markedly influencing the incidence. This article focuses on new issues leading to improved understanding of the pathophysiology and mechanisms of SVDs after surgery. New approaches directed at prophylaxis and acute therapy of SVDs are also discussed.

Aged↗
PubMed1996

Epidural analgesia for labour and delivery: fentanyl or sufentanil?

PURPOSE: The highly lipid soluble opioids, fentanyl and sufentanil, are used in combination with local anaesthetics with/without epinephrine to provide epidural analgesia during labour and delivery. Our aim was to determine whether wither opioid was superior when used with low dose local anaesthetic. METHODS: In a double-blind study patients were randomized to two epidural infusion groups: Group I (n = 50) fentanyl 2 micrograms.ml-1 with bupivacaine 0.015% and epinephrine 2 micrograms.ml-1, Group II(n = 50) sufentanil 1 microgram.ml-1 with bupivacaine 0.015% and epinephrine 2 micrograms.ml-1. Following a 20 ml bolus of the study solution an infusion was started at 10 ml.h-1. To achieve analgesia patients could receive two boluses of 5 ml of the study solution and if analgesia was still inadequate, a further 5 ml bupivacaine 0.25% was used. Pain and overall satisfaction were assessed with a 10-point visual scale. Plasma samples obtained from the mother at the time the infusion was discontinued and from the umbilical cord vein at delivery were assayed to determine opioid concentration. RESULTS: Pain scores were greater for Group I than for Group II patients throughout the first and second stages of labour (P = 0.002). More patients in Group I (42%) requested a dose of bupivacaine 0.25% than in Group II (6%) (P < 0.001) and the total dose of bupivacaine given to Group I patients was greater than that of Group II, 26.0 +/- 22.0 mg vs. 13.4 +/- 12.6 mg, P = 0.005. There were no differences with respect to first or second stage duration, incidence of side effects, infusion duration, outcome of labour or neonatal Apgar scores. There was no opioid accumulation in either maternal or foetal blood. CONCLUSION: Epidural opioid infusion with very low dose bupivacaine (0.015%) achieved an overall high level of patient satisfaction in both groups without serious maternal or neonatal side effects. At the fentanyl-to-sufentanil ratio used here patients receiving sufentanil had lower pain scores and substantially fewer patients required bupivacaine rescue.

Analgesia, Epidural↗
PubMed1996

Value of perioperative Doppler echocardiography in patients undergoing major lung resection.

BACKGROUND: The effects of major lung resection on right heart function have not been well established. Our goal was to evaluate these effects using serial Doppler echocardiography in the perioperative period. METHODS: In 86 patients undergoing lobectomy (n = 47) and pneumonectomy (n = 39), we examined the effects of pulmonary resection on perioperative changes in right heart function by transthoracic echocardiography. Serial echocardiograms were performed preoperatively, on postoperative day 1, and again between postoperative days 2 and 6 (median, 3 days) to evaluate cardiovascular function and to estimate right ventricular systolic pressure by the tricuspid regurgitation jet Doppler velocity method. RESULTS: Right or left atrial size, right atrial pressure, and estimated right ventricular systolic pressure did not differ between groups on the preoperative or postoperative day 1 examinations. However, on postoperative days 2 through 6 patients who underwent pneumonectomy had higher (mean +/- standard deviation) right ventricular systolic pressure values than lobectomy patients (31 +/- 15 versus 25 +/- 10 mm Hg, respectively; p < 0.05 by analysis of variance). In the subset of patients with percent predicted forced expiratory volume in 1 second less than 60% undergoing pneumonectomy (9/39), preoperative right ventricular systolic pressure was inversely correlated with percent predicted forced expiratory volume in 1 second values (r = -0.78; p < 0.04). This correlation was not significant in corresponding lobectomy patients. Postoperative right ventricular enlargement determined by echocardiography occurred with similar frequency in both groups and was associated with poor short-term prognosis in patients in whom severe respiratory failure developed. CONCLUSIONS: Preoperative indices of right heart function were within the normal range in both groups. Pneumonectomy but not lobectomy was associated with mild postoperative pulmonary hypertension that was not accompanied by significant right ventricular systolic dysfunction. Postoperative echocardiography may be useful to evaluate right heart function in critically ill patients after lung resection.

Adult↗
PubMed1996

Symptomatic tachydysrhythmias after esophagectomy: incidence and outcome measures.

BACKGROUND: Supraventricular tachydysrhythmias (SVT) after esophageal operations for carcinoma occur frequently and may be associated with increased morbidity. Prospective data on the etiology, incidence, and importance of these dysrhythmias are sparse. METHODS: In 100 consecutive patients undergoing esophagectomy without prior history of atrial dysrhythmias or receiving antiarrhythmics, we prospectively examined the effects of predefined risk factors by history and pulmonary function on the 30-day incidence of symptomatic postoperative SVT, need for intensive care unit admission, and mortality rate. RESULTS: Symptomatic postoperative SVT occurred in 13 (13%) of the 100 patients studied at a median of 3 days after operation and was accompanied by hypotension in 9/13 (69%). Univariate correlates of SVT were older age (p = 0.03), perioperative use of theophylline (p = 0.044), and a low carbon monoxide diffusion capacity (measured in 56% of patients) on preoperative pulmonary function. Patients in whom SVT developed had a higher rate of intensive care unit admission (p = 0.0001) and a longer hospital stay (p = 0.036). Although patients in whom SVT developed had a higher (p = 0.013) 30-day mortality rate, SVT was not the direct cause of death. CONCLUSIONS: These prospective data show that the true incidence of symptomatic SVT within 30 days of esophagectomy is lower than previously reported. Occurrence of SVT was associated with significant morbidity. Older age was the strongest predictor of SVT after esophagectomy. In high-risk patients, continued monitoring (48 to 72 hours) and early interventions to decrease the incidence of postoperative SVT may improve overall surgical outcomes.

Age Factors↗