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Biomedical subjects

J M Bernard

Publications and source records attributed to J M Bernard.

At least 73 records · Page 4Linked to original sources

Systemic haemodynamic and metabolic effects of deliberate hypotension with isoflurane anaesthesia or sodium nitroprusside during total hip arthroplasty.

Isoflurane (ISO) was examined as an alternative hypotensive agent to nitroprusside (SNP) in 16 patients (mean age: 60 years) anaesthetized for total hip arthroplasty. MAP was decreased to 50 per cent of the awake level by infusion of SNP in Group I (n = 8) and with ISO in Group II (n = 8). Fentanyl (10-16 micrograms X kg-1) was administered to both groups. Haemodynamic measurements were repeated in the lateral position before, during and after hypotension. Polygeline and fresh frozen plasma were infused throughout the study period in volumes sufficient to maintain pulmonary capillary wedge pressure in the 7-9 mmHg range. The MAP decrease was the same in both groups, as were perioperative blood replacement (mean 500 ml), and postoperative haematocrits. Total perioperative fluid replacement was higher (p less than 0.01) in Group I (mean 2500 ml) than in Group II (mean 1300 ml). Venous tone was more affected by SNP than by ISO. ISO decreased the systemic vascular resistance index and oxygen consumption (VO2) without any change in CI or in Qs/Qt, in contrast to SNP which increased CI, VO2 and Qs/Qt.

Adult↗

Synthesis of conjugates between luteinizing hormone releasing hormone (LH-RH) and N-acetyl-muramyl-L-alanyl-D-isoglutamine (MDP) models of totally synthetic vaccines.

Two glycopeptides associating the aminoacid sequence of LH-RH with MDP were prepared, using a Lys residue as a linker. These conjugates, N alpha MDP N epsilon (LH-RH)-Lys and N alpha MDP N epsilon (LH-RH)-Lys-NH2 obtained by condensation of fragments were synthesized by liquid as well as solid phase methods. Both compounds were able to induce anti LH-RH antibodies and immunological castration. They retained the immuno-adjuvant activity of MDP. Such antigen-adjuvant constructs, devoid of carrier and obtained by chemically defined and reproducible synthetic methods could offer suitable tools for structure-activity relationship studies aiming at defining synthetic vaccines.

Acetylmuramyl-Alanyl-Isoglutamine↗

Peroperative hypothermia prevention.

Peroperative thermal losses were studied in 28 patients (mean age 64 years) operated for a total hip prosthesis under controlled hypotension. The patients were split into four groups according to the method of hypothermia prevention used: reflective blanket, heating humidifier of inhaled gases, combination of both techniques or no prevention at all. The thermal loss was quicker and more intense in the last group. The superiority of one prevention method over another could not be demonstrated, but the urgency of its implementation proved to be essential.

Humans↗

Induction of murine macrophage tumoricidal activity and treatment of experimental pulmonary metastases by liposomes containing lipophilic muramyl dipeptide analogs.

The ability of three members of a new class of lipophilic muramyl dipeptide derivative to induce murine macrophage tumoricidal activity after liposomal incorporation was investigated. Liposomes containing the glycerol dipalmitate (GDP) derivatives of N-acetylmuramyl-L-alanyl-D-isoglutamine, N-acetylmuramyl-L-alanyl-D-glutamine-n-butyl ester, and N-acetylmuramyl-D-alanyl-D-isoglutamine were 5000, 2000, and greater than 10,000-fold more potent than the free muramyl dipeptides in inducing peritoneal macrophage tumoricidal activity in vitro. In situ activation of peritoneal macrophage tumoricidal activity showed that liposomal muramyl dipeptide-GDP derivatives were more potent than free hydrosoluble or sonicated muramyl dipeptide-GDP preparations. In situ induction of alveolar macrophage tumoricidal activity after i.v. treatment was observed with liposomes containing muramyl dipeptide-GDP derivatives, but not with hydrosoluble or sonicated lipophilic derivatives. Liposomes containing muramyl dipeptide-GDP derivatives were therapeutically active against experimentally induced pulmonary B16 melanoma tumors in C57BL/6 mice. These results demonstrate that when incorporated within liposomes this class of lipophilic muramyl dipeptide derivative is a potent inducer of macrophage tumoricidal activity both in vitro and in situ, and possesses antitumor activity in therapeutic treatment protocols.

Acetylmuramyl-Alanyl-Isoglutamine↗

Hypotensive actions of diltiazem and nitroprusside compared during fentanyl anaesthesia for total hip arthroplasty.

The potential for inducing hypotension during fentanyl anaesthesia by administering either diltiazem (n = 7) or sodium nitroprusside (n = 7) was investigated during total hip arthroplasty. Haemodynamic variables were obtained in the lateral position before, during and after administration of the hypotensive agent. Diltiazem 0.15 mg X kg-1 given as an IV bolus followed by a 12.5 +/- 3 micrograms X kg-1 X min-1 continuous infusion decreased mean arterial pressure (MAP) from 77 +/- 11 mmHg to 63 +/- 16 mmHg (p less than 0.05) while other haemodynamic parameters showed only minor and insignificant changes. Hypotension continued for at least 30 min after the cessation of diltiazem. With sodium nitroprusside MAP decreased immediately from 81 +/- 11 mmHg to 59 +/- 9 mmHg (p less than 0.01) and rapidly returned to its control value after cessation of the infusion. CI and Qs/Qt rose significantly (p less than 0.05) while the systemic vascular resistance index (SVRI) (p less than 0.01) and pulmonary vascular resistance index (PVRI) (p less than 0.05) fell significantly. The haemodynamic profile was significantly different between hypotensive agents for MAP (p less than 0.02), heart rate (HR) (p less than 0.01), SVRI (p less than 0.05), and PVRI (p less than 0.05). HR was lower with diltiazem than with nitroprusside. A bradycardia less than 50 beats/min was observed in five patients in the diltiazem group. MAP, SVRI and PVRI were lower with nitroprusside than with diltiazem. Diltiazem can induce and maintain moderate hypotension without tachycardia and decreased cardiac output in humans during fentanyl anaesthesia but the modulation of the level of arterial pressure and the depression of atrioventricular conduction are unpredictable.

Aged↗

[Hemodynamic effect of the clamping of the carotid in the surgically treated coronary patient].

To determine both the incidence of myocardial ischaemia and haemodynamic response to carotid cross-clamping in coronary artery disease, 30 patients undergoing carotid endarterectomy were studied with a clear history of effort related disabling angina pectoris. Myocardial ischaemia was detected by a recording of lead CM5 of the electrocardiogram. A radial arterial and a thermodilution pulmonary catheter were inserted to obtain haemodynamic measurements before and after carotid cross-clamping and unclamping. Anaesthesia was induced with increments of thiopental, fentanyl 6 micrograms X kg-1 and pancuronium. Additional fentanyl (2 micrograms X kg-1) was injected before skin incision and before carotid cross-clamping. Carotid cross-clamping results in a significant increase in both mean arterial blood pressure and capillary wedge pressure. Two patients experienced myocardial ischaemia with ST segment depression during carotid cross-clamping. Nitroglycerin infusion led to the improvement of ST segment depression. When halothane was additionally administered to patients who developed hypertension in response to carotid cross-clamping, arterial blood pressure returned to normal value. These results indicate that carotid cross-clamping increases determinants of myocardial oxygen demand and may cause myocardial ischaemia in patients suffering from angina pectoris.

Aged↗

Roles of fentanyl and nitroglycerin in prevention of myocardial ischemia associated with laryngoscopy and tracheal intubation in patients undergoing operations of short duration.

The purpose of this study was to evaluate intravenous nitroglycerin given during induction of anesthesia as a means for prevention of myocardial ischemia and hemodynamic changes associated with induction, laryngoscopy, and intubation, in patients with stable angina scheduled for vascular operations of moderate duration. Forty-six patients were randomly assigned to receive either fentanyl, 3 micrograms/kg (group 1, n = 6), fentanyl, 8 micrograms/kg (group 2, n = 20), or fentanyl 3 micrograms/kg plus a continuous intravenous nitroglycerin infusion, 0.9 microgram X kg-1 X min-1 (group 3, n = 20), in addition to thiopental-pancuronium anesthetic induction, prior to laryngoscopy and intubation. The criteria for recognizing myocardial ischemia were the following: horizontal or downsloping ST segment depression equal to or greater than 1 mV, and/or ventricular arrhythmia, on CM5 recording. In group 1, myocardial ischemia occurred during laryngoscopy and intubation in four patients, and mean blood pressure (MBP), heart rate, and mean pulmonary wedge pressure (PCWP) increased significantly (P less than 0.05). Despite greater stability in MBP and heart rate in group 2, myocardial ischemia still occurred in four patients (not significantly different from group 1). Nitroglycerin added to low-dose fentanyl (group 3) produced significant reduction in myocardial ischemia (1/20) when compared with group 1 (P less than 0.01), and significantly greater stability in PCWP during laryngoscopy and intubation in comparison to groups 1 and 2. In patients with stable angina undergoing operations of short duration, the use of nitroglycerin infusion and low-dose fentanyl significantly decreases the incidence of myocardial ischemia associated with induction of anesthesia and tracheal intubation.

Aged↗

[Is automatic oscillometric measurement of blood pressure reliable in hypotension?].

The reliability of an automatic oscillometric device for measurement of blood pressure (BP) was assessed in a large range of BP values during intraoperative normotension and induced hypotension. Direct BP measurements were carried out with a radial catheter. Data were compared with those obtained with the oscillometric device placed on the opposite arm. Nine patients were studied, undergoing 234 measurements of BP ranging from 55 to 208 mmHg (7.3 to 27.7 kPa) for systolic blood pressure (Pasys), from 32 to 130 mmHg (4.3 to 17.3 kPa) for diastolic blood pressure (Padia) and from 36 to 154 mmHg (4.8 to 20.5 kPa) for mean blood pressure (Pa). Good correlation between the two techniques was found for Pasys measurements recorded during both normotension and hypotension (r = 0.93; p less than 0.01). 92% of the values recorded with the oscillometric device were lower than those measured invasively. In the other cases (8% of the data), the mean difference between the two techniques was 5.5 mmHg (0.7 kPa). When BP values lower than 90 mmHg (12 kPa) for Pasys, 60 mmHg (8 kPa) for Padia and 70 mmHg (9,3 kPa) for Pa were considered individually, the correlation coefficients were 0.83, 0.73 and 0.77 respectively. These findings suggested that the oscillometric method can be considered as relatively suitable for monitoring moderate hypotension induced by vasodilators. The invasive technique must however remain the method of choice during profound hypotension.

Anesthesia, General↗

Activation of alveolar macrophage tumoricidal activity and eradication of experimental metastases by freeze-dried liposomes containing a new lipophilic muramyl dipeptide derivative.

The ability of a member of a new class of lipophilic muramyl dipeptide (MDP) derivative, muramyl dipeptide-glyceryldipalmitate (MDP-GDP), to induce alveolar macrophage cytotoxic activity in vitro towards B16 melanoma cells when incorporated into two types of liposome was studied. MDP-GDP incorporated into conventionally prepared liposomes formulated from distearoylphosphatidylcholine and phosphatidylserine (7:3 molar ratio) was 10-fold more effective than liposomes containing MDP, and 7000-fold more effective than free MDP in inducing macrophage cytotoxic activity. MDP-GDP incorporated into freeze-dried liposomes was 50,000- to 100,000-fold more effective than free MDP in inducing such activity. Freeze-dried liposomes containing MDP-GDP were efficiently localized in the lungs of normal mice, and induced cytotoxic activity in the alveolar macrophages. Such liposomes were able to significantly reduce the pulmonary metastatic burden of mice carrying the B16 melanoma. These data provide evidence that this class of lipophilic MDP derivative, when incorporated into freeze-dried liposomes, is a potent inducer of macrophage cytotoxic activity in vitro and in situ, and has antitumor activity in vivo. In addition, the use of a freeze-drying procedure allows the preparation and long-term storage of reproducible liposome formulations.

Acetylmuramyl-Alanyl-Isoglutamine↗

Activation of macrophage cytostatic and cytotoxic activity in vitro by liposomes containing a new lipophilic muramyl peptide derivative, MDP-L-alanyl-cholesterol (MTP-CHOL).

The ability of liposomes containing a new lipophilic muramyl peptide derivative, MDP-L-alanyl-cholesterol (MTP-CHOL), to induce peritoneal macrophage cytostatic activity and alveolar macrophage cytotoxic activity toward tumor cell targets in vitro was determined. MTP-CHOL was shown to be efficiently incorporated and subsequently retained in distearoylphosphatidylcholine/phosphatidylserine liposomes (DSPC/PS; 7:3 molar ratio), whereas hydrosoluble muramyl dipeptide (MDP) was rapidly lost due to leakage. Liposomes containing MTP-CHOL were able to stimulate mouse peritoneal macrophage cytostatic activity under conditions where free MDP was without effect. MTP-CHOL incorporated into liposomes was approximately eightfold more effective than liposomes containing entrapped MDP and 7,400-fold more effective than free MDP in inducing rat alveolar macrophage cytotoxic activity. These results provide evidence that the coupling of MDP to a lipophilic molecule, cholesterol, results in the formation of a viable liposome formulation that is a potent inducer of macrophage-mediated antitumor activity.

Acetylmuramyl-Alanyl-Isoglutamine↗