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Biomedical subjects

A Girard

Publications and source records attributed to A Girard.

At least 73 records · Page 4Linked to original sources

Immunoreactive beta-endorphin increases after an aspartame chocolate drink in healthy human subjects.

It has been claimed that sucrose intake induces a rise in beta-endorphins. In an attempt to discriminate between the sensorial and metabolic effects of sucrose intake in this process, the effects of two chocolate drinks were compared: one sweetened with 50 g of sucrose, the other with 80 mg of aspartame. Plasma beta-endorphin concentrations were more elevated after the aspartame drink than after sucrose or fasting, while insulin increased after drinking as much with aspartame as with sucrose. We suggest that the increase in beta-endorphin after aspartame edulcorated chocolate is related with insulin secretion in the absence of marked changes in blood glucose or with a direct effect of aspartame itself on beta-endorphin liberation.

Adolescent↗

Soluble CD8, IL-2 receptor, and tumor necrosis factor-alpha levels in steroid-resistant acute graft-versus-host disease. Relation with subsequent response to anti-IL-2 receptor monoclonal antibody treatment.

Serial determination of soluble CD8 (sCD8), soluble IL-2 receptors (sIL-2R), and tumor necrosis factor-alpha serum levels were performed in bone marrow transplant patients upon initiation, day 0 (D0) and at D10 of an anti-IL-2 receptor (alpha chain) monoclonal antibody (B-B10) in vivo treatment for steroid-resistant grade greater than or equal to 2 acute graft-versus-host disease (aGVHD). D0 and D10 sCD8 serum levels correlated strongly with response to B-B10 treatment (p = .003 and .001, respectively); 76% of the patients with D0 sCD8 levels less than 500 U/ml responded favorably to B-B10 treatment, versus only a 30% response if the sCD8 levels were greater than 500 U/ml (p = .02). Likewise, D0 tumor necrosis factor-alpha levels significantly correlated with subsequent response to B-B10 treatment (p = .03). D0 sIL-2R levels were not significantly different in B-B10-responsive and nonresponsive aGVHD patients. These results suggest that the serial determination of sCD8 and TNF serum levels could provide valuable predictive information as to steroid-resistant aGVHD responsiveness to anti-IL-2R treatment.

Adolescent↗

Effects of respiration on blood pressure and heart rate variability in humans.

1. Non-invasive continuous finger blood pressure (BP) measurement and a spectral technique based on the Fourier transform (FT) were recently combined to quantify short-term fluctuations in haemodynamic variables. 2. Systolic BP (SBP) recording combined low frequency (LF, Mayer waves) plus high frequency (HF, respiratory) oscillations. The presence of HF oscillations of SBP probably reflects fluctuations in cardiac output. Heart rate (HR) also exhibited a combination of low and HF (respiratory) oscillations. The vagus nerve mediates the efferent control of the respiratory sinus arrhythmia (RSA). 3. During controlled breathing in a supine position, a change in SBP is associated with an opposite consequent change in HR. Respiratory sinus arrhythmia could therefore depend on the baroreceptor-HR response to underlying SBP oscillations. 4. The fast regulation of R-R interval by SBP through the baroreceptor-HR reflex may explain why the respiratory variations in the diastolic BP are small.

Blood Pressure↗

Physical and dynamic characteristics of DC ablation in relation to the type of energy delivery and catheter design.

We evaluated and compared the in vitro characteristics of direct current ablation using high energy ablation (Hewlett-Packard defibrillator) and a new form of low energy ablation (low energy ablation power supply, Cardiac Recorders, UK). Two new catheters with a large distal electrode have been recently introduced for catheter ablation: a low energy 7F bipolar catheter (Bard) with a contoured distal electrode, and a 7F deflectable catheter with a 4-mm tip (Mansfield). In vitro studies were carried out in a large tank filled with physiological saline while recording voltage, current, and pressure. High speed cinematography at 32,000 frames per second (Cordin, Utah) was done to assess the dynamic behavior of the vapor globe with both systems of energy delivery. We evaluated shocks of 50, 100, 150, 200, and 300 joules with the conventional system, and shocks of 10, 15, 20, 30, and 40 joules with the new system, and also compared the effects of varying catheter design with both systems of energy delivery. The conventional system using high energy showed significant arcing and increases in pressure. Low energy direct current ablation produces nonarcing shocks with 20 joules or less, and significantly less vapor globe and gas formation during arcing shocks, with a shorter duration of increase in pressure. This new system using low energy direct current may reduce the risk and complications reported with high energy ablations.

Cardiology↗

In vitro and in vivo effects within the coronary sinus of nonarcing and arcing shocks using a new system of low-energy DC ablation.

DC shocks within the coronary sinus have been abandoned because of the risk of cardiac rupture and tamponade. Catheter ablation using DC energy to electrodes straddling the ostium of the coronary sinus, when used clinically, has been reported to result in cardiac tamponade in as many as 16% of patients. A new system of energy delivery maximizes voltage while decreasing the undesirable effects caused by barotrauma. This system includes 1) a low-energy ablation power supply with a brief time-constant capacitive discharge that delivers up to 40 J and 3,000 V and 2) a low-energy ablation catheter with a contoured distal electrode. We performed in vitro and in vivo studies of this new system and compared arcing shocks with nonarcing shocks. Ablations were performed using unipolar distal shocks (D) and unipolar shocks to both electrodes made electrically common (P-D). In vitro studies were done in a large tank filled with physiological saline while recording voltage, current, and pressure. High-speed cinematography (32,000 frames/sec) of shocks of 10-40 J permitted detailed analysis of the vapor globe. Anodal shocks of less than 20 J showed no arcing or only minimal vapor globe formation. For D and P-D anodal shocks of 40 J, the diameters of the vapor globe were 31 and 22 mm, respectively, corresponding to pressure recordings of 11 and 4.9 atm. The pressure rise lasted less than 50 mu sec. In vivo studies involved 18 dogs that received nonarcing shocks (one to six shocks of 15 J) and 18 dogs that received arcing shocks (one to three shocks of 40 J). Each group was divided between D and P-D shocks; catheter ablation was performed at a mean +/- SEM distance of 2.94 +/- 0.92 cm within the coronary sinus. All dogs tolerated the procedure without cardiac rupture or tamponade. When killed 2-4 days later, the dogs had edema and hyperemia or hemorrhage in the area of the coronary sinus. We compared the effects of multiple (three to six) nonarcing shocks with the effects of one to three arcing shocks. Disruption or rupture of the coronary sinus within the epicardial fat space occurred in two of 12 dogs (17%) with multiple nonarcing shocks but in 13 of 18 dogs (72%) with arcing shocks (p less than 0.003). Occlusion of the coronary sinus occurred in two of 12 dogs (17%) with multiple nonarcing shocks and in nine of 18 dogs (50%) with arcing shocks (p less than 0.06).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Serum lipid abnormalities in heart transplant recipients: predominance of HDL2-like particles in the HDL pattern.

Accelerated coronary atherosclerosis is a major risk limiting long-term survival after heart transplantation and is commonly associated with dyslipoproteinemia even in subjects who were not dyslipoproteinemic before intervention. The purpose of this study was to analyse the abnormalities in the lipid profiles of 2 different groups of heart-transplanted males: 18 subjects with underlying ischemic heart disease (IHD) and 19 subjects with non-obstructive cardiomyopathy of unknown aetiology (CM). Both groups were compared to 33 healthy males. All patients were under immunosuppressive therapy including prednisone, cyclosporin A and azathioprine. A moderate hyperlipidemia was found in all transplant recipients, associated with high HDL-cholesterol concentrations in the CM group (1.80 +/- 0.37 vs. 1.29 +/- 0.23 mmol/l) and normal HDL-cholesterol levels in the IHD group (1.40 +/- 0.23 mmol/l). HDL subfractionation showed a marked increase in HDL2-cholesterol (CM: 1.12 +/- 0.32; IHD: 0.69 +/- 0.28; control: 0.40 +/- 0.17 mmol/l) while HDL3-cholesterol was significantly lower than in the control group. Analysis of HDL particle sizes showed in all transplant subjects an increase of an intermediate size particle HDL2a (diameter 9.0 +/- 0.10 nm) which is a minor form in control subjects. In the CM group, both the common HDL2b (10.2 +/- 0.13 nm) and HDL2a were abundant in 13 of 17 patients. The pattern was more heterogeneous in the IHD group but witnessed to a high frequency of HDL2a particles either alone (5/14) or associated with larger HDL2b (4/14) or with small HDL3 (4/14).(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiomyopathies↗

Platelet phosphatidylcholine turnover in experimental hypertension.

To gain insight into the membrane alteration that could account for the hyperresponsiveness of platelets in hypertension, we have investigated whether, in resting platelets of hypertensive rats, the metabolism of phospholipids was modified. Because preliminary results indicated a specific acceleration of phosphatidylcholine turnover in spontaneously hypertensive rats, the possible relation between such an abnormality and hypertension was investigated by studying phosphorus-32 labeling of phosphatidylcholine (taken as an index of its turnover) in various experimental models of hypertension. The data showed that phosphatidylcholine turnover 1) was considerably increased in platelets from spontaneously hypertensive (even at the prehypertensive stage) and stroke-prone rats compared with Wistar or Wistar-Kyoto control rats, 2) did not differ between deoxycorticosterone-salt-treated hypertensive and control rats, and 3) was increased in Dahl salt-sensitive rats fed a high NaCl diet (hence hypertensive rats), compared with either the rats fed a low NaCl diet or the salt-resistant rats. These results indicate that an increase in phosphatidylcholine turnover is a consequence of neither hypertension nor high salt intake and appears likely to be of genetic origin. These data allow us to suggest the existence, in platelets, of a relation between phosphatidylcholine turnover, free cytoplasmic Ca2+, and responsiveness to stimuli. Because phosphatidylcholine is assumed to participate in signal transduction, an increase in its turnover in platelets might be considered as a primary membrane abnormality that, in primary hypertension, results in platelet hyperresponsiveness.

Animals↗

[Increased phosphorylations of proteins involved in the expression of the physiologic response of platelets in SHR rats].

In primary hypertension, phospholipase C (PLC) is hypersensitive in several target tissues (platelets, vascular smooth muscle cells, aortic fibroblasts). Protein kinase C (PKC) and myosin light chain kinase (MLCK), which are physiologically activated by PLC-triggered second messengers (diacylglycerol and Ca2+ ions, respectively), phosphorylate specific proteins closely involved in the cell functional responses. In this study, we have examined and compared between platelets of spontaneously hypertensive rats (SHR) and their normotensive controls Wistar-Kyoto (WKY), the patterns of protein phosphorylation obtained either with the receptor-mediated agonist thrombin (i.e. which acts via PLC) or with direct activators of the protein kinases, PKC and MLCK. Activation by thrombin of 32P-prelabeled platelets induced incorporation of radioactivity into two proteins, P20 (myosin light chain) and P47. The curves obtained when platelets were challenged with either increasing doses of thrombin (0.025-0.3 U/ml) for 20 sec or with a low dose of the agent (0.1 U/ml) for up to 1 min, revealed that phosphorylation of the target proteins of PKC (P47) and of MLCK (P20) were significantly enhanced in platelets of SHR compared to WKY. In contrast, direct activation of PKC by phorbol ester and of MLCK by the calcium ionophore A23187 evoked the selective phosphorylation of the respective target proteins, P47 and P20, to a similar extent in platelets of SHR and WKY. Taken together, these results demonstrate that a physiological agonist (thrombin) induces an enhanced phosphorylation of intracellular proteins in platelets of SHR.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Cell proliferation in human cerebral tumors. In vivo study of 45 cases by incorporation of 5-iododesoxyuridine].

A method to study the proliferation of human brain tumors, is presented. Non radioactive 5-Iododeoxyuridine (2.4 gr) infused over a 24 hours period is detected in situ on histologic section by an immunological technique (peroxidase-anti-peroxidase) using a specific anti-Iododeoxyuridine antibody. This exploration utilised in 45 patients is easy, reliable and harmless. All cells which enter in S phase of cellular cycle during the infusion are labelled. So the cellular kinetics of all the brain tumor cells (malignant cells, inflammatory stroma reaction cells, reactive astrocytes, endothelial and muscular cells of the vessels) are detected on the same histological section, as well as all the others proliferative cells of the body (leukocytes, primitive tumor of the metastatic brain localisation...) if multiples biopsies are done. 8 of 9 gliomas of low histological malignancy (grade I and II) have a slow cellular kinetic. The 23 astrocytomas of different histological malignancy (grade III and IV) have variable proliferative speed (7 very fast, 8 fast and 8 slow). Only the large cells of the pinealoma are very proliferative, the lymphoid stroma is quiescent. The 5 metastasis have a slow to very fast kinetic without correlation with the cellular differentiation except in one case (important differentiation and slow cellular proliferation). The 5 lymphoma cells kinetics are well correlated with the histologic differentiation (3 large cells poor differentiated lymphomas and very fast kinetic, 2 better differentiated and slower proliferation). The 2 meningiomas proliferate slowly. The biochemical and histopathological grounds of the presented method and the limits of quantification are discussed. This method is compared with this using Bromodeoxyuridine. The correlation between proliferation and histologic malignancy is analysed. The use of cytokinetic results for therapeutic and prognosis need further statistical anatomoclinical studies.

Adult↗

Obstructive ureteropathy following radiation therapy for carcinoma of the cervix.

Between January 1959 and December 1986, 10 of 328 patients (3%) treated with curative intent using primary radiation therapy for carcinoma of the cervix developed obstructive ureteropathy due to fibrosis. The mean age of the patients with obstructive ureteropathy was 45 years and the median time to obstruction was 26 months. The obstruction was unilateral in 8 cases and involved the parametrial portion of the ureter in at least 5 cases. No predisposing risk factor was found to be associated with the development of obstructive ureteropathy. After corrective surgery, renal function remained normal in 8 patients, and resolution of the hydronephrosis occurred in 4 patients.

Adenocarcinoma↗

In vitro activity of CP-65,207, a new penem antimicrobial agent, in comparison with those of other agents.

CP-65,207 is a new parenteral penem antibiotic with a broad spectrum that includes gram-positive, gram-negative, and anaerobic microorganisms, with MICs for 90% (MIC90s) of the majority of 1,101 clinical pathogens tested being less than or equal to 1 microgram/ml. The compound was from 10- to 100-fold more active than cefoxitin and broad-spectrum cephalosporins against gram-positive bacteria and anaerobes. CP-65,207 was less active than imipenem for staphylococci, group A streptococci, and Enterococcus faecalis. Against members of the family Enterobacteriaceae, CP-65,207 was in general 100-fold more active than cefoxitin, 5- to 10-fold more active than broad-spectrum cephalosporins, and 2-fold more active than imipenem. Fresh clinical isolates that were resistant to broad-spectrum cephalosporins were highly susceptible to CP-65,207 and imipenem (MIC90, 1 microgram/ml). Isolates of Enterococcus faecalis, Serratia marcescens, and anaerobic Peptococcus spp. had MIC90s of 8, 2, and 3.12 micrograms/ml, respectively. CP-65,207 was not very active against methicillin-resistant staphylococci or Pseudomonas aeruginosa. Killing kinetics showed that against some strains CP-65,207 is rapidly bactericidal at concentrations well below those required to achieve a similar degree of killing with cefotaxime, ceftazidime, and ceftriaxone. CP-65,207 was only slightly susceptible to hydrolysis by type I cephalosporinases and TEM-1, SHV-1, and PSE-2 plasmid-encoded enzymes. It had the highest affinity for penicillin-binding proteins 2, 1A, 1B, and 3 in cell-free preparations of Escherichia coli W-7.

Anti-Bacterial Agents↗

[Value of transcranial Doppler in the monitoring of aneurysmal subarachnoid hemorrhage treated with calcium inhibitors].

Fifty four patients (33 male and 21 female, mean age 47) with spontaneous aneurysmal subarachnoid hemorrhages have been tested by repeated TCD: 25 of them were systematically administered intravenous Nimodipine when admitted at hospital, the 29 others constituted a reference group. There was no statistically significant difference between the two groups of patients for age, sex, initial clinical status, importance of bleeding at CT scan, localization of aneurysm or existence of an angiospasm, whether clinically symptomatic or not. In 72% of the cases, TCD allowed to prove the existence of an angiospasm when higher flow velocity was registered in cranial basal arteries. There was no significant difference between the two groups. The final clinical status of the patients seemed to be more favourable in the treated group. Yet it did not appear to be directly linked to the existence of a spasm or not. This argued in favour of a non-univocal mechanism of action of Nimodipine.

Brain↗

Defective phosphoinositide metabolism in primary hypertension.

An increase in free cytosolic calcium content has been reported in essential hypertension. Since within the membrane, the phosphoinositides participate in the control of cell calcium homeostasis, we investigated whether impaired phosphoinositide metabolism could account for the calcium handling abnormality observed in hypertensives. In erythrocyte membranes of hypertensives the activity of kinases involved in polyphosphoinositide formation appears to be impaired and could be related to the alteration in calcium handling binding capacity and ATP-dependent calcium transport. In platelets of hypertensives, the hyperactivity of phospholipase C (observed even in the absence of calcium in the external medium) is likely to be responsible for the hypersensitivity of cells to various agonists. These observations are consistent with the hypothesis that in cells from hypertensives, a membrane defect linked to phosphoinositide metabolism is involved in the overall calcium handling defect.

Animals↗

Brain metastases with an unknown primary: a clinical perspective.

A review of 43 patients with cerebral metastases, an unknown primary, and no other sites of metastases is presented. 27/43 (62.7%) had solitary metastases and 37.2% (16/43) had multiple metastases. Surgical treatment involved complete resection in 30.2%, subtotal resection in 37.2% and biopsy alone or no surgical procedure in the remainder. 39/43 patients underwent whole brain irradiation with the majority receiving 3,000-4,000 rads/10-20 fractions. Overall survival was 52% at six months and 20% at one year, and was significantly better in patients with solitary as opposed to multiple metastases (p less than 0.03). A failure analysis including autopsy data demonstrates that (28/41) 68.3% of patients died of progressive intracranial disease without extracerebral metastases. Implications for treatment strategies are discussed.

Actuarial Analysis↗

Enhanced antibacterial resistance in neutropenic mice treated with human recombinant interleukin-1 beta.

Human Recombinant IL-1 was investigated for its ability to increase non-specific resistance to Staphylococcus aureus in neutropenic mice. Mice, rendered neutropenic with cyclophosphamide and then administered IL-1 intraperitoneally, demonstrated enhanced resistance to subsequent challenge with S. aureus as measured by increased survival and bacterial clearance. No protective effects were observed with heat inactivated IL-1. Efficacy was observed only when both IL-1 and the subsequent bacterial challenge were administered into the same site. Despite the observed protective effects, animals treated with IL-1 did not have increased numbers of blood leukocytes or peritoneal phagocytes prior to infection or at the times coincident with bacterial clearance. Based upon these observations, enhanced activity of resident macrophages may be responsible for the protective effects observed in IL-1 treated mice.

Agranulocytosis↗