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Biomedical subjects

P Simon

Publications and source records attributed to P Simon.

At least 19 recordsLinked to original sources

5-HT1A receptor agonists prevent in rats the yawning and penile erections induced by direct dopamine agonists.

The new compound (+) S-20499, an amino chromane derivative (8[-4[N-(5-methoxychromane-3yl)N-propyl]aminobutyl] azaspiro[4-5] décane-7,9 dione), is a high affinity full 5-HT1A agonist. We have investigated its effects on dopaminergic transmission. (+) S-20499 displayed a 10(-8) M affinity for D2 dopamine (DA) receptors, 100 fold lower than for 5-HT1A receptors. The hypothermic effect of the drug was reversed by haloperidol in mice, suggesting that it behaves as a direct dopamine agonist. However, increasing doses of (+) S-20499 induced neither yawning nor penile erections, which constitute characteristic responses of direct DA agonists administered at low doses. In addition, (+) S-20499 prevented the apomorphine (100 micrograms/kg SC) induced yawning and penile erections. This inhibition appears to result from the stimulation of 5-HT1A receptors since it is an effect shared by both buspirone (from 5 mg/kg) and 8-OH-DPAT (from 0.10 mg/kg). In addition, when rats are treated with the 5-HT1A receptor antagonist tertatolol (2-5 mg/kg; SC), increasing doses of (+) S-20499 elicit the expected yawns and penile erections. It is concluded that the 5-HT1A agonist property opposes to that of D2 dopamine receptor stimulation with regard to yawning and penile erections.

8-Hydroxy-2-(di-n-propylamino)tetralin

Translocation (6;16) in a case of granulosa cell tumor of the ovary.

We performed a cytogenetic study of an ovarian granulosa cell tumor (GCT). Tumor cells showed a translocation (6;16); the full karyotype was 45,XX-6,dic(6;16)(q11;q22)/44,XX,-6,-22,dic(6;16)(q11;q22),-22/46,XX,- 6,dic(6;16)(q11;q22), +dic(6;16)(q11;q22). This is the second case of GCT with structural changes of chromosome 6 leading to loss of 6q material.

Adult

Sulpiride anxiogenic-like effect inhibition by a D1 dopamine receptor antagonist.

The increased latency to explore a white compartment from a black one into which a mouse has been introduced, appears to be correlated with its anxiety level. In this test, the D2 specific dopamine receptor antagonist (+/-) sulpiride dose dependently (5-40) mg kg-1 i.p.) increased this latency. This effect was suppressed by the D1 specific dopamine receptor antagonist SCH 23390 (25 micrograms kg-1 s.c.) which intrinsically displayed an apparent anxiolytic effect.

Animals

The preferential expansion of functional CD4+ lymphocyte populations in vitro.

We describe a simple and inexpensive chemical procedure for the selective expansion of human CD4+ lymphocytes. The method employs L-leucine methyl ester (LME) to deplete monocytes and large granular lymphocytes, as well as to inhibit growth of CD8+ lymphocytes. LME treatment eliminates granular cells, but most CD8+ lymphocytes, B-lymphocytes, and CD4+ lymphocytes remain. Peripheral blood mononuclear cells (PBMCs) from normal and HIV-positive individuals are treated with LME for 1 h at ambient temperature and cultured in the presence of IL-2 to expand the cell number. Stimulation with the T-cell mitogens concanavalin A, phytohemagglutinin, or OKT3 antibody augments lymphocyte expansion and within 1-3 weeks the culture is greatly enriched (90-100%) in CD4+ lymphocytes. LME-treated lymphocytes expand up to 10-fold during culture in the presence of IL-2 alone and up to 400-fold following treatment with T-cell mitogens. The immune function of LME-treated and expanded peripheral blood lymphocytes was examined using the response to the recall antigens tetanus toxoid and Candida albicans. Fresh PBMCs exposed to these recall antigens proliferated readily. Similarly, LME-treated lymphocytes following expansion responded to these recall antigens with good fidelity to the original PBMC response patterns in four of six donors. The expanded and LME-treated lymphocytes also exhibited good mitogen responses in three of three donors. The LME procedure allows for the simple and inexpensive generation of expanded, immunologically functional, CD4+ lymphocytes.

CD4-Positive T-Lymphocytes

Cardiac function, morphology and chromosomal aberrations in a calf with ectopia cordis cervicalis.

A male calf with ectopia cordis cervicalis inferior was investigated clinically, hemodynamically, and morphologically from the 3rd day of age until slaughter at the age of 22 months. Arterial hypertension (mean AOP 140 mm Hg), concentric myocardial hypertrophy and good ventricular contractility with normal valve function were found. Normal clinical condition at rest (cardiac output 48 l/min in the 600 kg bullock), but cyanosis and dyspnea during physical exercise were observed. Variations in the large vessels, such as persistence of the right cranial caval vein and one common pulmonary vein emptying into the left atrium, were found. Abrupt caliber differences of large arterial vessels together with a right angled aortic arch were observed, presumably contributing to increased afterload. The cytogenetic analysis showed the presence of a small marker chromosome leading to a chromosome number of 61 in a fraction of metaphases (mosaicism). Moreover, chromosome breakages were observed in many cells. From the 5 cows which were inseminated, 3 became pregnant. Ectopia cordis was not observed in any offspring. We conclude that in this animal compensated cardiac insufficiency with peripheral hypertension was established.

Animals

[Transesophageal echocardiography from the surgical viewpoint].

Following the development of new techniques in echocardiography and especially of Doppler color flow imaging, a new dimension of cardiac surgery has been brought about. The use of transesophageal probes facilitates routine surgery to be performed without interferences and, also, comparability between repeated ultrasonic measurements. Originally, echocardiography was mainly applied for quality control by comparing pre- and postoperative echocardiograms. Now it is equally important in perioperative strategy planning guiding the surgeon's decision throughout the operation as well as in cardiac emergencies. Using intraoperative echocardiography routinely in cardiac surgery establishes a more and more close cooperation between surgeons, cardiologists, and anesthesiologists. In order to evaluate the clinical relevance of echo findings, they have to be repeatedly correlated to surgical realities and to long term results of clinical outcome.

Adult

[Value of multiple cortical perforations for the rehabilitation of massive deep-frozen bone allografts. Experimental study in sheep].

Incorporation of massive cortical bone allografts in human is slow and remains incomplete. Late biopsies of implanted allografts or histological studies of explanted allografts always show the partial substitution of necrotic bone by new bone from the host. The aim of the present study was to evaluate the effect of drilling the massive deep-frozen cortical allografts in order to induce osteogenesis. Thirteen sheep were operated on and a standard segment of the proximal ulna was removed and the gap filled either by an unperforated allograft or by a perforated one. Based on histological and microradiographic examination, a quite complete substitution of the perforated allografts was observed but in this model no statistically significant difference was observed between perforated and unperforated allografts. Further study is needed to assess the effect of the perforations.

Animals

Cytokines and platelet-activating factor in human inflamed colonic mucosa.

Colonic biopsy specimens from patients with active ulcerative colitis and controls were incubated for four hours in the presence or absence of calcium ionophore or antihuman immunoglobulin E (IgE). Platelet-activating factor (PAF) was determined in the tissue by aggregation assay after extraction with 80% ethanol. PAF was not detected in normal mucosa, whereas A23187 and antihuman IgE stimulated its activity: mean +/- SE, 43.2 +/- 8.6 and 33.0 +/- 6.1 pg/10 mg wet weight, respectively. In active ulcerative colitis, A23187 and antihuman IgE induced significantly higher stimulation of PAF synthesis compared to their effects on normal mucosa. The enhanced stimulation of PAF induced by A23187 was dose-dependently inhibited by sulphasalazine, 5-aminosalicylic acid and prednisolone, but not by sulfapyridine. Colonic interleukin-1 content and release during 24 h of culture were significantly higher in patients with active ulcerative colitis and Crohn's disease compared to normal subjects. Prednisolone significantly and dose-dependently inhibited interleukin-1 release. These results suggest that colonic generation of PAF and interleukin-1 are elevated in patients with inflammatory bowel disease and, thus, may have a role in its pathogenesis. Pharmacological suppression of colonic PAF and interleukin-1 production may have beneficial therapeutic effects.

Aminosalicylic Acids

Aprotinin decreases release of 6-keto-prostaglandin F1 alpha and increases release of thromboxane B2 in cultured human umbilical vein endothelial cells.

Use of the proteinase inhibitor aprotinin significantly improves hemostasis and reduces bleeding after operations in which extracorporeal circulation is used. The mechanism of action, however, has been only partially clarified. In this work we investigated whether aprotinin influenced the production and release of the eicosanoids prostacyclin, measured as the stable metabolite 6-keto-prostaglandin F1 alpha, and thromboxane A2, measured as the stable metabolite thromboxane B2, from endothelial cells. Human umbilical vein endothelial cells were incubated with different concentrations of aprotinin (5.5, 20, 55, and 100 mumol/L). The levels of 6-keto-prostaglandin F1 alpha and thromboxane B2 were measured at baseline and after thrombin stimulation. A concentration-dependent effect of aprotinin on 6-keto-prostaglandin F1 alpha synthesis was demonstrated. After incubation with 100 mumol/L of aprotinin, a 90% reduction in 6-keto-prostaglandin F1 alpha production was seen (31.69 versus 307.44 picograms per million cells; p less than 0.001). Conversely, thromboxane B2 production showed a 345% increase after incubation with aprotinin (287.80 versus 83.82 picograms per million cells; p less than 0.0001). Since 6-keto-prostaglandin F1 alpha inhibits and thromboxane B2 strongly enhances platelet aggregation, it appears that one mechanism of the clinically observed effectiveness of aprotinin lies in the altered ratio of 6-keto-prostaglandin F1 alpha: thromboxane B2 in endothelial cells, which leads to enhanced platelet aggregation and improved vessel sealing.

6-Ketoprostaglandin F1 alpha

Aprotinin increases release of von Willebrand factor in cultured human umbilical vein endothelial cells.

Through the perioperative administration of the proteinase inhibitor aprotinin, hemostasis can be improved and postoperative bleeding reduced after cardiac operations. The mechanism of action has been only partially clarified. The goal of our study was to investigate the influence of aprotinin on the synthesis of von Willebrand factor (vWF) in human endothelial cells. Human umbilical vein endothelial cells (HUVEC) were cultivated in vitro and incubated with different aprotinin concentrations (55, 100, and 215 mol/L). With all investigated aprotinin concentrations, there was an increase in vWF synthesis compared with basal secretion (p less than 0.001). When the HUVEC were preincubated with aprotinin and stimulated with thrombin, there was a further significant increase in vWF synthesis. HUVEC that, were first incubated with aprotinin and then stimulated with thrombin demonstrated a significant increase in vWF synthesis compared with basal secretion in nonincubated cells (p less than 0.0001). Also, compared with the cells that had received thrombin stimulation alone, the combination of aprotinin incubation and thrombin stimulation led to a significantly higher vWF concentration (p less than 0.05). Because vWF is necessary for the interaction with platelet factor glycoprotein Ib and platelet adhesion, the demonstrated increase in vWF synthesis could be one of the mechanisms of action of aprotinin leading to its blood-sparing effect.

Aprotinin

Multimedia for clinical education in myocardial perfusion imaging.

Interactive multimedia has many advantages as a presentation medium for diagnostic imaging case studies, particularly for teaching digital imaging techniques such as myocardial perfusion imaging. Multimedia documents may incorporate interactive audiovisual presentations, sophisticated diagnostic images, anatomical illustrations, and text in medical instructional materials. The article describes a multimedia teaching atlas of SPECT and planar myocardial perfusion imaging delivered on Apple Macintosh II microcomputers, and discusses some of the advantages of delivering medical educational materials with interactive multimedia techniques.

Computer-Assisted Instruction

[Collection of fetal cord blood for karyotyping].

Cordocentesis was performed in 234 pregnancies (241 fetuses) for rapid karyotyping. The indication was in 86% of cases: abnormal ultrasound. The abnormality encountered were IUGR (85 fetuses) or morphologic abnormality of the pregnancy (130 fetuses). The other indications were maternal mosaicism, mosaicism in cultured amniotic cells, maternal age (late booking), fragile X syndrome, confirmation of abnormal karyotype obtained by amniocentesis. The fetal karyotype was established in 97.5% (6 failures), 18 karyotypes were abnormal in the group "abnormal ultrasound" (208 pregnancies, 8.6%; 215 fetuses, 8.3%). No maternal complication were observed, there were 6 fetal losses (2.5%).

Blood Specimen Collection

Transesophageal echocardiography in the emergency surgical management of patients with aortic dissection.

The diagnostic accuracy and benefit of transesophageal echocardiography were investigated in 32 patients with suspected aortic dissection. Results of transesophageal echocardiography were compared with surgical assessment. The Stanford classification was used for differentiation of dissection type. Examination time was 5 to 15 minutes. Twenty-eight patients were correctly identified to have aortic dissection; four patients had nondissecting aneurysms of the ascending aorta. Both sensitivity and specificity for detection of aortic dissection were 100%. Type of dissection was misdiagnosed in one patient. Classification of dissection type was correct in 96%. The primary entry site was correctly identified in 25 patients (89%). Aortic regurgitation was found in 57% of patients. Pericardial effusion was detected in 21%, with tamponade in one patient. Myocardial infarction was suggested by transesophageal echocardiography in 7%, and 14% had significantly reduced left ventricular function. Eight patients underwent operation based on transesophageal echocardiography alone. Intraoperative transesophageal echocardiography, performed in 20 patients, verified retrograde flow in the true lumen after femoral cannulation. Transesophageal echocardiography documented postrepair persistence of the intimal flap in aortic segments that were not operated on in all patients. Secondary tears and flow in the false lumen were detected in 35% of patients. We conclude that transesophageal echocardiography allows expedient and accurate diagnosis and classification of aortic dissection, and we recommend it as the primary bedside diagnostic modality. It can especially identify patients requiring surgical intervention without further delay caused by other diagnostic procedures.

Adult

Effects of coronary artery bypass grafting on global and regional myocardial function. An intraoperative echocardiographic assessment.

The immediate effect of coronary artery bypass grafting on global and regional myocardial function was studied by means of epicardial two-dimensional echocardiography during operations in 20 patients. Echocardiograms were recorded before cardiopulmonary bypass and 5 and 30 minutes after bypass. Global left ventricular function was expressed as percent short-axis area change and regional function as percent fractional area change. Segments were classified according to their baseline function as normal (percent fractional area change greater than 40%), moderately hypokinetic (percent fractional area change 21% to 40%), or severely dysfunctional (percent fractional area change less than 20%). Percent short-axis area change was significantly reduced immediately after cardiopulmonary bypass (from 42.0% +/- 4.6% to 34.9% +/- 3.0%, p less than 0.05) but had returned to baseline 30 minutes after bypass (42.6% +/- 4.0%). Similarly, function of normal and moderately hypokinetic segments decreased significantly immediately after cardiopulmonary bypass (normal segments: percent fractional area change 56% +/- 0.9% before bypass to 42.3% +/- 1.5% after bypass, p less than 0.0001; moderately hypokinetic segments: 31.0% +/- 0.9% to 25.1% +/- 1.4%, p less than 0.002). Both normal and moderately hypokinetic areas regained baseline function by 30 minutes after bypass (normal segments: 53.4% +/- 1.6%; moderately hypokinetic segments: 35.4% +/- 2.0%). In contrast, severely dysfunctional segments were found to be significantly improved immediately after bypass (14.7% +/- 0.9% before bypass to 27.7% +/- 2.1% after bypass, p less than 0.0001). This improvement was maintained 30 minutes after bypass (22.8% +/- 1.5%, p less than 0.001). We conclude that coronary revascularization exhibits an immediate beneficial effect on chronically underperfused myocardium having severely depressed baseline function. However, in normal and moderately hypokinetic areas, the depressant effects of global ischemia and reperfusion prevail in the immediate postbypass period, leading to a global depression of cardiac function.

Angina Pectoris

Oxygen measurements in endometrial and trophoblastic tissues during early pregnancy.

Placental and endometrial partial pressures of oxygen (PO2) were measured using a polarographic oxygen electrode during the first trimester of pregnancy. Between 8-10 weeks' gestation, placental PO2 levels were significantly lower (P less than .001) than endometrial levels. A significant (P less than .001) increase was observed for placental PO2 values measured at 12-13 weeks compared with those obtained at 8-10 weeks. We suggest that the increase of placental PO2 at the end of the first trimester is related to the establishment of continuous maternal blood flow in the intervillous space.

Endometrium

[Bone density in 20 black African young adults of the Bantu race is identical to that in subjects of white race].

Bone mineral content (BMC in g) as well as bone mineral density (BMD in g/cm2) were measured by dual photon absorptiometry in 20 black africans and 20 white individuals of the same age and sex. The BMC of african males, as well as their body mass index (BMI), were significantly less than those of the whites. In contrast, neither BMD nor the ratio of BMC to BMI differed between the two groups. These results suggest that morphotype plays a greater role than the ethnic factor in the determination of bone mass in the young adult.

Adult