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Biomedical subjects

A Girard

Publications and source records attributed to A Girard.

At least 55 records · Page 3Linked to original sources

Cardiovascular reactivity to a new mental stress test: the maze test.

The response to the maze test was studied in 31 subjects on no medication, including seven subjects with mild essential hypertension. Beat-by-beat finger blood pressure (BP) was measured with a Finapres device. Pulse interval from which heart rate (HR) was derived was obtained from the BP signal. A period of 5 min baseline was used to define resting levels of systolic BP and HR using 20-s averaged values for the calculation of the 95% confidence limit of the two variables. The average test duration was 10 min. During this period a series of video-displayed mazes had to be solved with easy mazes preceding difficult ones. No subject had been exposed to the test before. The maximal BP elevation associated with the test was 27 mmHg. The HR response averaged 11 beats/min. Significant elevations were observed for half the test duration. No significant relationship between these two responses was observed and some subjects exhibited isolated systolic BP or HR responses. When indices obtained during this active mental stress were compared to resting values, positive correlations were observed. When the resting standard deviation (SD) of systolic BP was higher the systolic response was greater. A similar relationship was observed for HR. In addition, when the systolic BP level at rest was higher, the systolic BP reactivity index was greater. However, systolic BP or HR at baseline were not predictive of the systolic BP or HR responses. This study demonstrates the applicability of a new test to assess cardiovascular reactivity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Spectrum analysis of heart rate and arterial systolic pressure after heart transplantation in children].

The aim was to examine the short-term variability of blood pressure (BP) and heart rate (HR) in 19 children who had received heart transplants and in 8 normal control children. BP was determined by a finger arterial pressure device. We examined the power spectra for HR and systolic blood pressure (SBP) in the supine and standing posture. In the transplanted children we could distinguish two groups (groups A and B) in whom HR variability differed, though in both it was greatly reduced compared to controls (group C). In group A there were no significant fluctuations in the mid frequency (MF) range for HF. Gain of the relationship between SBP and HR was very low and there were virtually no HR changes associated with passive tilting. By contrast, in group B transplant patients the HR variability, as assessed by standard deviation was about half that of normal controls. The power spectra attenuation was greater in the high frequency (HF) than in the MF bands. On standing the latter became enhanced, but not the HF variability. The findings suggest some reinnervation involving cardiac sympathetic fibres to a greater degree than the fast-responding vagal fibres. Time since operation was a critical factor for reinnervation since all subjects from group B were transplanted more than 44 months prior to the recording. We conclude that in a proportion of children who have received heart transplantation there is a delayed reinnervation of the heart, which probably involves sympathetic effectors rather than the vagus.

Age Factors↗

[Reproducibility of short-term variability indicators of blood pressure].

The aim of this study was to estimate the degree of reproducibility of blood pressure (BP) variability profile between 2 clinic visits. We recruited 15 untreated subjects (6 hypertensives, 9 normotensives) from the outpatient clinic. This group had undergone at least one BP measurement by the same investigator (A.G.). The subjects underwent 5-min BP monitoring (Finapres) during standing and after a rest in a supine position, at 10 AM and at 23 degrees C in a quiet room. Measurements were repeated after 7 days. A fast Fourier transform algorithm was used for analysis. There was no order effect with no difference between visits 1 and 2. Coefficients of variation (CV) for systolic BP, diastolic BP and heart rate were 9, 6 and 12%. High CVs of 20% were observed for the overall variability (total power) and the low frequency (LF, Mayer wave) component of BP. However the normalized LF (LF/total area) exhibited a acceptable CV of 15%. In conclusion the BP variability profile differences observed between visits might reflect intrasubject effect. This should be considered for assessing BP variability profile and for drug trial design.

Adult↗

Phase II study of lonidamine plus radiotherapy in the treatment of brain metastases.

Twenty-nine patients received the cytotoxic radiosensitizing agent lonidamine before, during, and after cranial irradiation for brain metastases. One patient was ineligible (meningioma). In 28 eligible patients, median survival was 29 weeks (range, 2 to > 220 weeks). Nine patients (32%) survived > 1 year and 3 (11%) survived > 2 years. The major toxic effects of lonidamine were myalgias, nausea and vomiting, somnolence, and ototoxicity. There was no evidence that radiation skin toxicity or cerebral toxicity was increased by the addition of lonidamine. None of the patients experienced shrinkage of their extracerebral disease on lonidamine. Median survival duration in this study was at the upper limit of that reported in the literature for radiation alone, and the proportion of 2 year survivors was also higher than usual for radiation alone. Hence, further studies may be warranted.

Adult↗

Effects of the cold pressor test on short-term fluctuations of finger arterial blood pressure and heart rate in normal subjects.

The effect of the cold pressor test on autonomic cardiovascular control was studied non-invasively by means of spectrum analysis of periodic heart rate and blood pressure fluctuations in ten normal subjects. Fast Fourier Transform algorithm based on a 256-point time series (sampling rate 2 Hz, i.e. 2-min and 8-s) was used to estimate the amplitude spectra of heart rate and blood pressure rhythmicity at the low frequency (70-140 mHz) and respiration related frequency (230-270 mHz) band. Respiration rate was controlled at 250 mHz. Auto- and cross-spectral techniques were used to determine the complex relationship between systolic blood pressure and heart rate fluctuations in the frequency domain. The spectral pattern of systolic and diastolic blood pressure showed a marked increment of the absolute and relative (100 multiplied with absolute value/total area under the curve of the amplitude spectrum from 15-500 mHz) low frequency component: control vs. cold pressor test--systolic blood pressure--absolute values (in [mmHg/Hz1/2]): 634.4 +/- 48.9 vs. 827.4 +/- 69.9*; relative values (in [%]): 26 +/- 2 vs. 32 +/- 2*; diastolic blood pressure--absolute values: 433.2 +/- 42.3 vs. 537.2 +/- 45.8*; relative values: 35 +/- 3 vs. 40 +/- 2*, (average +/- SEM, *P < 0.05). The cold pressor test induced no change in average heart rate; the absolute low frequency component in heart rate spectra increased clearly during the test: low frequency component (in [bpm/Hz1/2]): 586.9 +/- 89.9 vs. 712.0 +/- 91.4*, while the relative low frequency component did not change: 29 +/- 3 vs. 30 +/- 3.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Elevated high density lipoprotein concentrations in heart transplant recipients are related to impaired plasma cholesteryl ester transfer and hepatic lipase activity.

Accelerated atherosclerosis is a major complication of heart transplantation, and is frequently associated with a dyslipoproteinemia characterized by a paradoxical increase in HDL-cholesterol concentration. To define this abnormality, the lipoprotein profiles of 25 heart transplant recipients (HTR) were analyzed and compared with those of 26 control subjects. HDL, as separated on the basis of density in 3 subfractions, were increased in concentration: HDL2: +51%, HDL3a: +29%, HDL3b: +32%. HDL2 and HDL3a displayed an enrichment in surface components, phospholipids, unesterified cholesterol and apo E, leading to an increased size compared with subfractions of similar density in the controls. The major steps of plasma HDL metabolism were investigated: cholesterol esterification (LCAT activity), cholesteryl ester transfer to apo B-containing lipoproteins (CETP) and the hepatic hydrolysis of HDL components (HL activity). We demonstrated a partial deficiency in CETP (-28%) and hepatic lipase (-36%) activities with normal LCAT activity. Correlations in total study population (HTR plus controls) evidenced negative associations between CETP activity and HDL3a concentrations and between HL activity and HDL2-cholesterol as a percent of total HDL-cholesterol. Therapeutic agents used in post transplantation treatment such as glucocorticoids and/or cyclosporine may be speculated thus to affect both CETP and HL activities and, by arresting the HDL cycle in a CE-saturated state, do decrease the efficiency of reverse cholesterol extraction at the site of the graft.

Apolipoproteins↗

[Leukocyte depletion of blood products and post-transfusion infections].

The transmission of unwanted infection agents to patients, through white blood cells, in blood products is now well established. Therefore the leukodepletion procedure undertaken in blood banks is justified. Leukodepletion prior to transfusion prevents the transmission of leukocyte-associated viruses such as CMV, EBV and HTLV 1 and 2 of viruses present both in plasma and inside leukocytes such as HTLV 1 and 2 viruses and B 19 parvovirus. The mechanism of the immunosuppressive effect of transfusion is still uncertain. The risks of transmitting bacterial diseases through blood transfusions is also a well-known source of concern, particularly the transmission of Yersinia Enterocolitica. However such an event seems to be prevented through leukocyte depletion by filtration when these procedures are performed after a hold of whole blood at 22 degrees C for 6 to no longer than 24 hours. Leukocyte-free blood components prepared by filtration may have a sufficiently reduced rate of infection to provide adequate prophylaxis. In any case the final number of leukocytes should be < or = 10(6) per unit of blood product. Leukocyte filtration must be performed before the onset of a disintegration process of granulocytes.

Bacterial Infections↗

The Head and Neck Radiotherapy Questionnaire: a morbidity/quality-of-life instrument for clinical trials of radiation therapy in locally advanced head and neck cancer.

PURPOSE: The purpose of this study was to develop and validate an instrument for clinical trials to measure radiation-related acute morbidity and quality of life from the perspective of patients with head and neck cancer (HNC) treated with radiotherapy. METHODS: The Head and Neck Radiotherapy Questionnaire (HNRQ) was developed by a panel of health care workers and patients, was pretested in a pilot study of HNC patients, and was validated in a randomized double-blind trial of concomitant fluorouracil (FUra) infusional therapy (1.2 g/m2 per 24 hours) or saline placebo administered for 72 hours in the first and third weeks of a 6 1/2-week course of radiation therapy. The HNRQ was validated against existing toxicity and performance status indices, all of which were measured weekly for the 6 1/2 weeks of treatment and for 4 weeks posttreatment. RESULTS: There were three a priori constructs: (1) that the HNRQ scores would conform to a shallow U-shaped pattern to reflect declining quality of life (increasing morbidity) during radiation and recovery posttreatment; (2) that the HNRQ would correlate with existing toxicity indices (World Health Organization [WHO] stomatitis, Byfield stomatitis, WHO skin toxicity, Eastern Cooperative Oncology Group [ECOG] and Karnofsky performance status); and (3) that the HNRQ would discriminate between FUra and placebo groups. The HNRQ and its domain scores all showed a change from baseline reflecting increased morbidity during radiation (analysis of variance [ANOVA], P < .00001). The HNRQ correlated well with all other indices (r > or = .60), and domain scores correlated best with other indices that assess the same symptom complex (eg, HNRQ skin domain and WHO skin toxicity index, r = .77). There was a significant difference in HNRQ scores between the FUra and placebo groups during radiation (ANOVA, P = .0007), and all HNRQ domains also discriminated between the treatment groups. CONCLUSION: The HNRQ is a valid measure of acute morbidity due to radiation therapy in patients with locally advanced HNC, and may be useful as an outcome measure for future clinical trials of radiation treatment strategies.

Carcinoma, Squamous Cell↗

[Pressure variability in the cold-pressure response test].

The effect of the immersion of the hand in ice water for 5 minutes on the short-term variability of blood pressure (BP) and heart rate (HR) was evaluated in 10 normal subjects. Indirect finger BP was measured by a non-invasive device (Finapres). Analogue-to-digital conversion of the BP was used to determine systolic, diastolic BP and HR every 0.5 second. The equidistant sampling allowed a direct spectral analysis using a fast Fourier transform algorithm on 256 point time series of a stationary period. BP was increased (+28 mmHg for systolic BP and +13 mmHg for diastolic BP) and an increased overall variability of BP and HR was observed during the cold pressor test. The increased areas under the curve of the systolic, diastolic BP and HR spectra were documented with the selective analysis of the two main components of the spectra: the increase in the oscillations of BP and HR during the test predominated in the 70-140 mHz region (+30% for systolic BP, +24% for DBP and +21% for HR), corresponding to Mayer waves. The high-frequency (respiratory) component of BP and HR variability was unchanged. The significant increase in the 10 second period oscillations of BP could reflect the cold-induced sympathetic vasoconstriction.

Adaptation, Physiological↗

Effects of plasmapheresis on short-term variability of blood pressure in healthy donors.

The acute effect of mild central hypovolaemia induced by plasmapheresis on the short-term variability of blood pressure and heart rate was evaluated in ten healthy donors. Indirect finger blood pressure was measured by a non-invasive device (Finapres). Analogue-to-digital conversion of the blood pressure was used to determine systolic, diastolic and mean blood pressure and heart rate every second. The equidistant sampling allowed a direct spectral analysis using a fast Fourier transform algorithm. Blood pressure and heart rate were maintained while an increased overall variability of blood pressure was observed after plasmapheresis. The increased total area under the curve of the systolic and diastolic blood pressure spectra was documented with the selective analysis of the three main components of the spectra: the increase in the oscillations of blood pressure following plasmapheresis predominated in the 66-129 mHz region, corresponding to Mayer waves. The spectral profile of HR was unaffected by plasmapheresis. The significant increase in the 10-s period oscillations of blood pressure after the mild central hypovolaemia could result from the unloading of cardiopulmonary (and arterial) baroreceptors which in turn could buffer the arterial pressure through sympathetic activation, detected on the systolic and diastolic pressure spectra in the low-frequency range.

Adult↗

Adoptive immunotherapy with bispecific antibodies: targeting through macrophages.

We report on two applications of bispecific antibodies to enhance the antitumoral function of human macrophages: (1) use of rhuIFN gamma (recombinant human IFN gamma) encapsulated in human red blood cells coated with anti-Fc gamma RI/anti-RhD+ bispecific antibodies to target and to activate human macrophages; encapsulated rhuIFN gamma was more potent than free IFN gamma in activating mature macrophages in vitro, demonstrating the efficacy of this delivery system to initiate in situ activation of macrophages and also to maintain a high antitumoral efficacy of macrophages with less side effects than after systemic injection of IFN gamma; (2) targeting of activated macrophages to tumours by bispecific antibodies directed against macrophage Fc gamma RI and against human adenocarcinoma antigen; differentiated human macrophages became cytotoxic for human adenocarcinoma in vitro and in vivo (tumours implanted in nude mice) when activated by rhuIFN gamma; this effect was increased in the presence of bispecific antibodies. These two approaches were aimed at increasing the efficacy of cellular immunotherapies using activated macrophages as effector cells (macrophage-activated killer, or MAK), an adoptive therapy which we have developed. Bispecific antibodies could increase specific homing and activation of cytotoxic MAK effectors at tumour sites.

Antibodies↗

Spectral analysis of short-term blood pressure and heart rate variability in uremic patients.

Short-term fluctuations in blood pressure (BP) and heart rate (HR) were quantified to assess autonomic nervous system (ANS) dysfunction in six dialysis patients, compared to six control subjects of similar age. Indirect finger BP was measured by a Finapres device. Analog-to-digital conversion of the BP was used to determine systolic BP (SBP), diastolic BP (DBP) and HR every second. The equidistant sampling allowed a direct spectral analysis using a fast Fourier transform algorithm. Uremic patients exhibited reduced BP and HR short-term variabilities, with a dramatic reduction in the amplitude of the 0.1 Hz component (Mayer waves) of SBP and DBP spectra. Dialysis did not produce any consistent immediate improvement in the amplitude of the Mayer waves. Our study thus indicates impaired cardiovascular ANS function in uremic patients.

Adult↗

[Possible sexual transmission of hepatitis C virus].

The development of hepatitis C virus (HCV) serology has made it possible to identify high-risk populations. The predominant mode of contamination is parenteral, but the relative frequency of the so-called sporadic hepatitis C cannot be explained in this way, and this raises the question of possible sexual contamination. The risk of HCV being transmitted by sexual intercourse has been studied in 30 couples, each with one infected partner. Among the 30 HCV seropositive subjects, 18 were followed up for chronic hepatitis and 2 for haemophilia; 10 were recruited in sessions of blood donation. The other 30 partners were tested for HCV seropositivity and investigated for other possible risk factors by means of a questionnaire. Three of them had antibodies to HCV, but only one, whose partner had chronic hepatitis, showed no other source of contamination. The prevalence of HCV positivity was 3.3 percent overall and 5.5 percent in the chronic hepatitis group. Thus, the risk of HCV heterosexual contamination is low when compared with that of the other sexually transmitted diseases. However, the prevalence of HCV in this population seems to be 5 to 10 times higher on average than in the general population.

Adult↗

Compartmentalized system with membrane-bound glycerol kinase. Activity and product distribution versus asymmetrical substrate supply.

An artificial-membrane-bound glycerokinase chosen as a membrane-bound two-substrate-enzyme model has been used to separate two unequal compartments of a specially designed diffusion cell. An interesting feature is the asymmetry of compartments and the existence of a diffusion layer adjacent to only one face of the enzymic membrane. In such a situation the apparent enzyme activity and the product distribution in the system have been studied versus all the possibilities of combination of ATP and glycerol supply. Our approach has lead us to differentiate two different roles played by a diffusion layer adjacent to a permeable enzymic membrane. Depending on the spatial origin of the enzymic substrates (i.e. from which compartment they derive), the diffusion layer can play either the role of a passive additional resistance to that of the membrane or the role of a third compartment in which the reaction product can partially accumulate before splitting on both parts of the membrane. Our results mainly demonstrate that a membrane-bound enzyme activity and the resulting product distribution occurring in a compartmentalized system may be regulated by the cumulative effect due to the asymmetry in volumes of the compartments, the presence of a diffusion layer and the different possibilities of substrate supply. With the topography studied, which is close to that reported for many 'in vivo' situations, the product may be diffused lead to vectorial metabolism processes.

Enzymes, Immobilized↗

Effects of the converting enzyme inhibitor trandolapril on short-term variability of blood pressure in essential hypertension.

Short-term fluctuations in blood pressure and heart rate were analysed in a group of eight males with essential hypertension. Indirect finger blood pressure was measured by a non-invasive device (Finapres). Analogue-to-digital conversion of the blood pressure was used to determine systolic and diastolic blood pressure and heart rate every second. The equidistant sampling allowed a direct spectral analysis using a fast Fourier transformation algorithm. The effect of 7-day administration of the angiotensin converting enzyme inhibitor, transolapril (2 mg/day), was assessed in a double-blind, randomized, placebo-controlled cross-over study. After trandolapril there was a significant reduction in systolic blood pressure levels (-15 mmHg). The reduction in diastolic blood pressure did not reach significance. The standard deviation of systolic and diastolic blood pressure levels were significantly reduced (-20% and -22% for systolic and diastolic respectively). Neither average heart rate nor standard deviations of heart rate time series was affected by the angiotensin converting enzyme inhibitor. Spectral analysis of fluctuation in blood pressure showed a reduction in the variability underlying the standard deviation changes of systolic and diastolic blood pressure. Trandolapril selectively reduced the amplitude of systolic and diastolic oscillations in the 66-129 mHz region, corresponding to Mayer waves. The significant decrease in the 10 s period oscillations of blood pressure after chronic angiotensin converting enzyme blockade with trandolapril could reflect reduced sympathetic outflow to vascular smooth muscle.

Adult↗