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Biomedical subjects

A Simon

Publications and source records attributed to A Simon.

At least 253 records · Page 14Linked to original sources

Quantification of erythrocyte aggregation by blood echogenicity: a preliminary study.

Many techniques were proposed to assess erythrocyte aggregation in clinical and experimental investigations in view of in vitro determination. However no methodology until now is available to measure erythrocyte aggregation in flowing blood in vivo. High resolution ultrasonography provides an original way to quantify erythrocyte aggregation using the echogenicity of blood. We have developed and A-mode ultrasound scanner coupled with an oscilloscope and a computer allowing the analysis of ultrasonic signals produced by erythrocytes. A closed measurement chamber connected to a calibrated roller-type blood pump where blood was perfused was used. The echogenicity of blood was determined at different shear rates. Dextran, fibrinogen and other high molecular weight substances were added to increase erythrocyte aggregation. Changes in red blood concentration was also tested. An increase in blood echogenicity rate was observed at low shear. At a given shear rate blood echogenicity increased when fibrinogen or dextran were added. Such determination of the echogenicity of flowing blood in vitro will provide an approach to the quantification of erythrocyte aggregation in vivo circulation, especially in the veins where low shear rates are observed.

Biomechanical Phenomena↗

Amlodipine induces a flow and pressure-independent vasoactive effect on the brachial artery in hypertension.

1. The objectives of this study were to study the flow-dependent arterial reactivity and pressure-independent arterial compliance of the calcium antagonist amlodipine in hypertensive men. 2. Twenty-one hypertensive patients were randomized to receive 2 months treatment with placebo (n = 10) or 5-10 mg amlodipine (n = 11) once a day. Non-invasive measurement of brachial artery mean blood pressure, diameter and flow (pulsed Doppler) and compliance (arterial mechanography and logarithmic elastic model) were obtained before and after drug administration. Vasoreactivity was studied by means of response of the brachial artery during exclusion of the hand and hyperaemia post-ischaemia. 3. Compared with placebo, amlodipine reduced mean blood pressure (% change +/- s.e. mean 11 +/- 1% vs 4 +/- 3%, P < 0.05), and increased arterial compliance at prevailing pressure (44 +/- 13%, vs 1 +/- 8%, P < 0.05) and at isobaric pressure (26 +/- 10% vs -3 +/- 6%, P < 0.05). A significant % change increase from baseline in brachial artery diameter between placebo and amlodipine was observed at rest (-2 +/- 3 vs 8 +/- 3%; P < 0.05), after wrist occlusion (-3 +/- 3 vs 6 +/- 2%; P < 0.05) and during reactive hyperaemia (-5 +/- 3 vs 18 +/- 5%; P < 0.05). No significant differences between amlodipine and placebo groups were observed in blood velocity after forearm manoeuvres before and after treatment. 4. No differences were observed between groups in brachial flow-dependent vasodilation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Effect of 2 types of diet changes on dietary habits, body weight and cholesterol levels in high risk cardiovascular patients].

Several non-pharmacological interventions such as weight reduction in obese subjects or diet alteration in subjects having hypercholesterolemia have been shown to be effective in therapeutic trials. Our aim was to test the value of two different ways of teaching patients about their diet. From March 1, 1993, to May 30, 1994, 300 consecutive patients seen in a one-day care hospital were randomised into two groups. The 2 inclusion criteria were: 1) body mass index > 27 kg/m2 in men and > to 25 kg/m2 in women and/or 2) presence of a hypercholesterolemia defined by a total cholesterol > 6.5 mmol/l. Patients in the first group (C) were educated in a 20 to 50 minutes consultation tailored to their needs. Patients in the second group (CC) were given in addition a one-hour course about diet. The goal of the diet was to loss at least 3 kg of body weight and/or to have a cholesterol value below 6.5 mmol/l without treatment. All Patients were followed-up by the same 3 dietician nurses. An out-patient visit was planned at 3 months, and a recall letter was sent to the patients who missed their appointments. Among the 300 patients, 169 (55%) were seen at the 3-month outpatient visit. This proportion did not differ between the 2 groups. Knowledge on diet was assessed by the same 33-item self-administered questionnaire. At baseline scores were comparable between groups (16 vs 17). Scores improved more in the CC than in the C group both at the end of the teaching question (27 vs 23 in the CC and C group respectively, p < 0.001), and at 3 months (25 vs 23 in the CC and C group respectively; p < 0.001). Total cholesterol decreased below 6.5 mmol/l in 28% of the patients with dyslipidemia and a weight loss > 3 kg was observed in 32% of the obese subjects, but improvement did not differ between the 2 groups. We conclude that a specific one-hour course on diet is able to improve knowledge of patients more than a consultation alone, but that better knowledge did not result in improved alteration of risk factors at 3 months.

Adult↗

Platelet cytosolic calcium concentration, plasma lipids and hypertension.

OBJECTIVE: To study the relationship between high blood pressure and hyperlipidaemia and the cytosolic calcium concentration in unstimulated platelets, focusing on the effects of an alteration in membrane dynamics. MATERIALS AND METHODS: Basal cytosolic calcium concentrations were determined in the presence and the absence of a significant calcium influx in platelets of 47 untreated hypertensive patients and 26 normotensive subjects. Membrane microviscosity was investigated by fluorescence depolarization of diphenylhexatriene and trimethylaminodiphenylhexatriene. To study the influence of plasma factors, unstimulated platelets were loaded in the presence of plasma with Quin-2, which forms a relatively strong intracellular calcium buffer. The cytosolic calcium concentration was then determined at two extracellular calcium concentrations (1 mmol/l and in the absence of a Ca2+ influx). RESULTS: Irrespective of the external calcium concentration, the cytosolic calcium concentration increased significantly with diastolic blood pressure (P = 0.026 in the presence and P = 0.003 in the absence of Ca2+ influx) and with plasma triacylglycerols (P = 0.03 and 0.001, respectively). Multiple regression analysis indicated that the cytosolic Ca+ concentration was independently related to these two factors [Ca2+ = 35 + (18.6 +/- 4.6). In triacylglycerols (mmol/l) + (0.45 +/- 0.15) mmHg diastolic blood pressure; P < 0.001]. The relationship between the cytosolic calcium concentration and diphenylhexatriene or trimethylaminodiphenylhexatriene anisotropies was not independent of blood pressure and plasma triacylglycerol levels. CONCLUSIONS: The present results confirm the link between blood pressure and the platelet cytosolic calcium concentration and indicate that plasma triacylglycerols directly or indirectly modulate the ex vivo efficacy of platelet calcium storage and/or extrusion mechanisms. They could facilitate cell stimulation.

Blood Platelets↗

Alignment and sensitive detection of DNA by a moving interface.

In a process called "molecular combining," DNA molecules attached at one end to a solid surface were extended and aligned by a receding air-water interface and left to dry on the surface. Molecular combing was observed to extend the length of the bacteriophage lambda DNA molecule to 21.5 +/- 0.5 micrometers (unextended length, 16.2 micrometers). With the combing process, it was possible to (i) extend a chromosomal Escherichia coli DNA fragment (10(6) base pairs) and (ii) detect a minute quantity of DNA (10(3) molecules). These results open the way for a faster physical mapping of the genome and for the detection of small quantities of target DNA from a population of molecules.

DNA↗

Stimulated human gastric tumor cells (HGT) fail to synthesize eicosanoids.

HGT cells are a human gastric tumor cell line. Preliminary data have shown that HGT cells incorporate exogenous arachidonic acid (AA) in their membrane lipids. However, we found that HGT cells are unable to produce significant amounts of AA metabolites after stimulation with calcium ionophore A23187. Furthermore, no lipoxygenase activity was detected in crude HGT cell extracts by employing an assay monitoring the in vitro utilization of linoleic acid. The meaning of these results is discussed in respect of the role of eicosanoids during cell proliferation.

Calcimycin↗

Localization of cellular retinoid-binding proteins suggests specific roles for retinoids in the adult central nervous system.

Retinoic acid, the active metabolite of retinoids (vitamin A compounds), is thought to act as a gene regulator via ligand-activated transcription factors. In order to investigate possible roles of retinoids and retinoid-controlled gene expression in brain function, we have used immunohistochemistry to localize the possible presence of two intracellular retinoid-binding proteins, cellular retinol-binding protein type I and cellular retinoic acid-binding protein type I, in the adult rat central nervous system. We find a widespread, yet distinct, presence of these two binding proteins in the brain and spinal cord. Most of the immunoreactivity is neuronal, including cell somata, as well as dendritic and axonal processes and axon terminals. Cellular retinol-binding protein type I-immunoreactivity is also found in the walls of cerebral blood vessels, the meninges, the choroid plexus, certain ependymal cells, tanocytes and certain other glial elements. The cellular retinol-binding protein type I- and cellular retinoic acid-binding protein type I-immunoreactivity patterns appear to be almost exclusively non-overlapping. Very strong cellular retinol-binding protein type I-immunoreactivity is found in the dendritic layers of the hippocampal formation and dentate gyrus. Cellular retinol-binding protein type I-immunoreactivity is also present in layer 5 cortical pyramidal neurons and neurons in the glomerular layer of the olfactory bulb. Many other areas, e.g. hypothalamic nuclei and amygdala areas, contain networks of varicose cellular retinol-binding protein type I-immunoreactive nerve fibers. The medial amygdaloid nucleus contains strongly cellular retinol-binding protein type I-positive neurons. Cellular retinoic acid-binding protein type I-immunoreactivity is more restricted in the adult brain. Strong cellular retinoic acid-binding protein type I-immunoreactivity is, however, found in a population of medium-sized neurons scattered throughout the striatum, in neurons in the glomerular layer of the olfactory bulb, the olfactory nerve and in a group of nerve cells close to the third ventricle in hypothalamus. The remarkably selective patterns of cellular retinol-binding protein type I- and cellular retinoic acid-binding protein type I-immunoreactivity discovered in the adult rat brain suggest that retinoids have important roles as regulators of gene expression in normal brain function. The high levels of cellular retinol-binding protein type I-immunoreactivity found in hippocampus suggest that one such role might relate to brain plasticity.

Animals↗

The effect of estradiol depletion during the luteal phase on endometrial development.

OBJECTIVE: To examine whether luteal E2 is obligatory for obtaining an adequately developed endometrium. DESIGN: Survey of women with premature ovarian failure (POF) in a prospective, controlled, randomized study. SETTING: In vitro fertilization unit in a tertiary care university medical center. PATIENTS: Fourteen amenorrheic women with POF, candidates for oocyte donation, were divided into two distinct groups with seven women in each subgroup. INTERVENTIONS: Endometrial priming with a fixed dose of oral micronized E2, 4 mg/d for 14 days, was similarly performed in the study and the control groups. Progesterone replacement during the luteal phase was also identical in the two groups and was accomplished by IM P in oil, 50 mg/d for another 14 days. Only the control group continued to have the same E2 regimen during the luteal phase. MAIN OUTCOME MEASURES AND RESULTS: Follicular phase mean E2 levels as well as luteal phase mean P levels were similar in both groups. However, luteal E2 levels differed significantly between the study and the control groups (21 +/- 5 and 692 +/- 199 pg/mL, respectively; conversion factor to SI units, 3.671). Nevertheless, histologic evaluation of endometrial biopsies on days 21 and 26 were similar for both groups. Endometrial gland dating, using light microscopy in the study and the control groups, on day 21, was 19.1 +/- 0.8 and 18.4 +/- 0.5, respectively, and on day 26, 25.4 +/- 0.8 and 25.9 +/- 0.5, respectively. Dating of the stroma in the two biopsies was also similar in both groups. Moreover, transmission electron microscopy performed in two patients of the study group showed typical characteristics of a secretory endometrium. CONCLUSIONS: Luteal E2 depletion in the human does not seem to adversely affect the morphological developmental capacity of the endometrium. Our results suggest that E2 secretion by the corpus luteum in the human does not appear to be obligatory for the development of a normal secretory endometrium. The actual receptivity of the endometrium after such preparation needs to be evaluated.

Adult↗

The effect of progesterone administration in the follicular phase of an artificial cycle on endometrial morphology: a model of premature luteinization.

OBJECTIVE: To evaluate the effect of premature P administration on artificially prepared endometrium in women with ovarian failure. DESIGN: To mimic premature luteinization, patients with ovarian failure were treated with continuous estrogen and episodic P during the follicular phase of artificial cycles. SETTING: In vitro fertilization unit at a university hospital. PATIENTS: The study group included 16 patients with ovarian failure who were randomly divided into two groups. Group A (8 patients) was treated by episodic P administration during the artificial follicular phase on days 2 and 7 (12.5 mg of P in oil IM), and in group B (8 patients), P (6.25 mg) was added on days 3, 4, and 5. Another 16 patients (group C), age matched to the study group, were arbitrarily allocated to serve as controls and had standard preparatory cycles without P supplementation in the follicular phase. Serum E2 and P levels and endometrial biopsies were taken on days 14 and 26. RESULTS: Serum E2 levels were comparable between the study group (group A+B) and controls on both days 14 and 26. Although serum P levels did not differ between the groups on day 26, it was higher in the follicular phase of the study group than in the controls (1.9 +/- 4.0 and 0.2 +/- 0.1 ng/mL, respectively). In the study group, 8 of 16 patients demonstrated early secretory changes in the late follicular phase biopsies, and 9 of 16 women developed stromal-glandular discrepancy in the late luteal phase. This differed significantly from the controls in which only one late luteal biopsy was out of phase. CONCLUSIONS: Episodic surges of P during the follicular phase may result in impaired endometrial development that cannot be corrected by P supplementation during the luteal phase. This unique model provides evidence for the potential detrimental effect of premature P secretion in the follicular phase on endometrial function.

Adult↗

The use of vaginal tablets as a vehicle for steroid replacement in a donor oocyte program.

Nine women enrolled in the donor egg program received in a preparatory cycle 6 mg of E2 by vaginal tablets two times per day for the first 14 days, followed by a combined preparation of 6 mg of E2 and 50 mg of P as vaginal tablets, two times per day for another 14 days. Adequate serum levels of E2 and P and favorable sonographic endometrial thickness were achieved throughout the cycle in all patients. Eight endometrial biopsies taken on days 25 to 26 were independently assessed as being representative of day 25 +/- 2. One endometrial biopsy was out of phase. It is concluded that vaginal tablets of E2, followed by a combined preparation of vaginal tablets of E2 and P, is an effective method for establishing an appropriately developed endometrium in a donor oocyte program. Endometrial preparation in donor oocyte programs can be simplified by the use of these tablets.

Biopsy↗

A comparison between a standard and reduced dose of D-Trp-6-luteinizing hormone-releasing hormone administered after pituitary suppression for in-vitro fertilization.

A randomized prospective study was undertaken to compare low and standard luteinizing hormone-releasing hormone agonist (LHRHa) dosage used in combination with gonadotrophins in ovarian stimulation for in-vitro fertilization (IVF). A total of 42 ovulatory patients with mechanical infertility were administered 0.5 mg/day LHRHa (Decapeptyl) from day 21 of their cycles for 14 days. Following down-regulation, patients were randomly allocated to continue with the same dose of LHRHa (22 patients, group A) or to receive a lower dose of 0.1 mg/day LHRHa (20 patients, group B) during folliculogenesis. Luteal phase was supported by daily i.m. progesterone (50 mg) injections and human chorionic gonadotrophin (HCG; 1500 IU) every 4 days. Ovarian response, human menopausal gonadotrophin (HMG) dosage used for induction of ovulation, evidence of premature luteinization, and clinical and laboratory IVF outcome, were compared between groups A and B. The two groups were comparable in respect of: age (32.6 +/- 0.7 and 33.0 +/- 0.9 years), HMG dosage (33.0 +/- 1.6 and 36.0 +/- 2.5 ampoules), day of HCG (11.2 +/- 0.3 and 12.2 +/- 0.4), oocytes/patient (13.3 +/- 1.0 and 12.9 +/- 1.3), fertilization rate (68.5 and 65.2%), cleavage rate (95% for both), pregnancy/embryo transfer (32 and 35%) and implantation rate (10.8 and 10.5%), for groups A and B respectively. There was no evidence of premature luteinization or luteolysis in either group. It was concluded that lowering the dose of LHRHa to 0.1 mg/day during folliculogenesis had no adverse effect on ovarian response or clinical results. However, it had no advantage in reducing the HMG dose used for ovulation induction.

Adult↗

Defective oocytes as a possible cause of infertility in a beta-thalassaemia major patient.

Impaired reproduction is common among patients afflicted with beta-thalassaemia major and is attributed mainly to the deposition of haemosiderin in the pituitary gland and ovaries. In-vitro fertilization (IVF)--embryo transfer cycles including ovum donation cycles are described for the first time in a patient with beta-thalassaemia major. The patient's oocytes were not fertilized by the husband's sperm in repeated IVF attempts. However, when donated oocytes were used, in two consecutive cycles, most were fertilized by the husband, yielding pregnancies after each embryo transfer. It is suggested that in this case of beta-thalassaemia major, impaired oocyte function contributed to infertility. However, a possible association between thalassaemia major and defective oocytes should be tested on a basis of additional IVF-embryo transfer cycles in these patients.

Adult↗