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PubMedDate not supplied

[Antiphospholipid antibodies and cerebral ischemia].

Lupus anticoagulants (LAs) and anticardiolipin antibodies (ACAs) are acquired circulating immunoglobulins that cross-react with anionic and neural phospholipids. These factors may display anticoagulant properties in vitro by interfering with phospholipid-dependent coagulation tests. These antibodies are usually not associated with a bleeding tendency. In fact, paradoxically to their name, since the initial recognition they have been related to systemic and cerebral thromboembolisms, despite their in vitro "anticoagulant" properties. We report the clinical and laboratory findings in 4 LAs and ACAs positive patients with brain ischemia.

Adult↗
PubMed1975

Maternal and fetal hemodynamic effects of diazoxide.

Effects of diazoxide on systemic and uterine hemodynamics as well as on fetal circulation and blood respiratory gases were investigated in chronically instrumented pregnant sheep. Diazoxide was administered intravenously either to the ewe or directly to the fetus in doses calculated on the basis of body weight. Transfer of drug across placenta was also investigated. Results showed that: a) when injected into the mother, there was consistent hypotensive effect with increased cardiac output and decreased systemic vascular resistance; uterine blood flow might not change or might decrease slightly with moderate hypotension; when maternal systemic arterial pressure fell to critical closing pressure level, uterine flow decreased significantly; but despite these maternal changes, the fetal circulatory functions were not significantly altered; b) when injected into the fetus in doses up to 15 mg/kg, diazoxide failed to alter fetal circulation appreciably; c) diazoxide crossed the placenta when injected intoeither mother or fetus according to a definite gradient; fetal levels were always lower than maternal levels because of rapid loss of the drug by the fetus; d) moderate maternal and fetal hyperglycemia occurred after drug administration.

Animals↗
PubMed1988

Enzymatic barriers to peptide and protein absorption.

Continuing advances in biotechnology promise to provide a large number of peptides and proteins that would significantly expand the range of pharmaceuticals to treat diseases now poorly controlled. Even at this early stage, it is clear that the success of these entities as drugs of the future would depend, at least in part, on the success in overcoming the obstacles in their delivery. Chief among these are the ubiquitous enzymatic barriers. These include the site of administration, where the peptide is placed, the vascular endothelium that peptides must cross to enter the circulation, the blood that distributes the peptide to its target site, and the liver and kidneys where the peptide is metabolized and eliminated, respectively. The review examines: (1) the nature and efficiency of the enzymatic barriers in degrading peptides and proteins at various absorption sites, and (2) the strategies that can be used to perturb these barriers. These sites include the subcutaneous and intramuscular spaces and the intestinal, nasal, buccal, rectal, vaginal, and ocular surfaces.

Absorption↗
PubMed1988

Magnetic resonance imaging of the placenta in rhesus monkeys, Macaca mulatta.

Magnetic resonance imaging of the uterus of rhesus monkeys was performed at different stages of pregnancy. Spin-echo sequences localized the placental discs before and after gadolinium enhancement. Fast-scan sequences provided semiquantitative appreciation of placental hemodynamics. The paramagnetic agent enhanced the placenta, crossed into the fetal circulation, and was excreted in the fetal urinary bladder. Gd DTPA was also used to contrast the external contours of the fetus.

Animals↗
PubMed1978

Lymphocyte mitogenic factor in sera from patients with falciparum malaria.

To test for the presence of a lymphocyte mitogenic factor in malaria, sera were obtained from 10 patients with malaria (9 with falciparum and one with vivax), and 10 noninfected controls. The sera from the malarial patients caused an increased blastogenesis in mouse splenic lymphocyte cultures and inhibited hemagglutination between lipid-A-coated erythrocytes and lipid-A antibodies. None of the sera were positive using the limulus amebocyte lysate test. These results could be interpreted to demonstrate that patients with falciparum malaria have a circulating mitogen which cross-reacts with endotoxin. However, alternate explanations must be considered, including an hypothesis that antiglobulins and/or immune complexes in the sera of malarious patients both caused the blastogenesis of mouse spleen cells and inhibited hemagglutination to lipid-A antibodies.

Adult↗
PubMed1994

Maternal middle cerebral artery blood flow velocity variation with gestational age.

OBJECTIVE: To assess the variation of the maternal middle cerebral artery blood flow velocity with gestational age in a normotensive pregnant population. METHODS: Middle cerebral artery blood flow velocity was assessed transcranially in 154 normotensive pregnant women using a 2-MHz pulsed probe. We assessed maximum systolic, minimum diastolic, and mean velocity and resistance index. Subjects were classified into seven gestational age categories of 4-week intervals starting from 13 weeks. Analysis of variance was used to indicate a significant difference in cerebral blood flow velocity with gestational age, and Tukey test to assess the significance. RESULTS: Maximum systolic velocity fell significantly in the third trimester (P < .01) to the lowest value (62 cm/second). Minimum diastolic velocity did not change with gestational age (28 cm/second). Mean velocity fell significantly from 25-36 weeks. CONCLUSIONS: Systolic and mean maternal middle cerebral artery blood flow velocity fell significantly with advancing gestational age, even though diastolic velocity did not vary. These changes did not correlate with mean arterial pressure changes with gestational age.

Blood Flow Velocity↗
PubMed1994

Characterization of a factor IX variant with a glycine207 to glutamic acid mutation.

Factor IXTaipei9 is a factor IX variant from a hemophilia B patient with reduced levels of circulating protein molecules (cross-reacting material reduced, CRM). This variant contained a glycine (Gly) to glutamic acid (Glu) substitution at the 207th codon of mature factor IX. The functional consequences of the Gly-->Glu mutation in factor IXTaipei9 (IXG207E) were characterized in this study. Plasma-derived IXG207E exhibited a mobility similar to that of normal factor IX on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Its specific activity was estimated to be 3.5% that of the purified normal factor IX in a one-stage partial thromboplastin time assay (aPTT). Cleavage of factor IXG207E by factor XIa or factor VIIa-tissue factor complex appeared to be normal. When the calcium-dependent conformational change was examined by monitoring quenching of intrinsic fluorescence, both normal factor IX and IXG207E exhibited equivalent intrinsic fluorescence quenching. Activated factor IXG207E (IXaG207E) also binds antithrombin III equally as well as normal factor IXa. However, aberrant binding of the active site probe p-aminobenzamidine was observed for factor XIa-activated factor IXG207E, indicating that the active site pocket of the heavy chain of factor IXaG207E was abnormal. Moreover, the rate of activation of factor X by factor IXaG207E, as measured in a purified system using chromogenic substrates, was estimated to be 1/40 of that of normal factor IXa. A computer-modeled heavy-chain structure of factor IXa predicts a hydrophobic environment surrounding Gly-207 and this Gly forms a hydrogen bound to the active site serine-365. The molecular mechanism of the Gly-->Glu mutation in factor IXTaipei9 might result in the alteration of the microenvironment of the active site pocket which renders the active site serine-365 inaccessible to its substrate.

Benzamidines↗
PubMed1994

[Application of the warm heart surgery to the open heart surgery in children].

Application of the warm heart surgery to the children's open heart surgery has been reluctant, because keeping the operative field dry thought to be difficult. In this report, the clinical result of 22 cases of children's open heart surgery using warm heart surgery (Warm Group) was compared with that of other 25 cases using conventional cold cardioplegia (Cold Group). In warm group, rectal temperature was kept at 34 degrees C, continuous coronary perfusion rate was 3 ml/kg/min, and potassium ion concentration for inducing the initial cardiac arrest was 20 mEq/l, and the maintaining dose was 12-17 mEq/l. There were two deaths in Cold group. In warm group, keeping the operative field dry was not difficult by using the specially devised small sucker (2 mm diameter) and, if necessary, temporarily stopping the coronary perfusion (maximum for 7 min). Aorta cross cramping time/total extracorporeal circulation time, CK-MB at 1-POD and maximum dose of dopamine and dobutamine proved the better myocardial protection in warm group (p < 0.01). From this study, it was concluded that warm heart surgery can be applied for children with no difficulty, and showed superior myocardial protection.

Body Temperature↗
PubMed1993

[Surgical treatment of patent ductus arteriosus in the adult].

Ten patients over the age of 30 were operated on for isolated patent ductus arteriosus (PDA). Division was performed in 9 patients and ligation in only one. In two cases, the aorta had to be cross-clamped above and below the level of the ductus under normothermia because of massive bleeding. In another two patients with aneurysmal dilatation and calcification of the aortic side of the ductus, PDA was closed by aortic cross-clamping under LA-to-femoral-artery bypass with a centrifugal pump. Postoperatively, all patients are well and in NYHA class I. Therefore, in the adult, if the conventional method of division between ductus clamps is considered dangerous due to increased friability and atheromatous changes of the ductus and surrounding tissues, the ductus should be closed during aortic cross-clamping under assist circulation. In such a case, LA bypass is considered quite useful and safe.

Adult↗
PubMed1996

Transversal trans-septal biatrial approach for mitral valve surgery.

A surgical approach to the mitral valve is very important to visualize all valvular and subvalvular structures. We have used a transversal trans-septal biatrial approach in some mitral procedures. From January 1994 to May 1994, 11 patients were operated on using this technique. Patient ages ranged from 28 to 74 years. Five cases (45.5%) were cardiac reoperations and six (54.5%) were first operations. Three case (27.3%) were mitral reconstructions, 3 (27.3%) were mitral replacement due to mechanical mitral valve thrombosis, 1 (9.1%) as a result of bioprosthetic mitral valve degeneration, 4 (36.4%) were mitral valve replacements for calcified mitral valve disease one case (9.1%) was tricuspid valve replacement due to severe tricuspid insufficiency. There were 4 case (36.4%) of tricuspid valvuloplasties besides the mitral procedures. There was no operative mortality, and all patients preserved their preoperative cardiac rhythm. No important bleeding or supra-ventricular arrhythmias were seen in any case. Aortic cross-clamping and extracorporeal circulation times were comparable with the traditional approach through the left atrial alone. So, we think that this is a very easy and useful technique to expose the mitral valve during some procedures above it, overall when the left atrium is small and total visualization of the mitral is not possible with the traditional approach through the left atrial alone.

Adult↗
PubMed1995

ParaSight-F rapid manual diagnostic test of Plasmodium falciparum infection.

The ParaSight(R)-F test is a qualitative diagnostic test of Plasmodium falciparum, which is based on the detection by a monoclonal antibody of a species-specific soluble antigen (histidine-rich protein (HRP-II)) in whole blood and which can be performed without special equipment. A visual reading is given by a polyclonal antibody coupled with dye-loaded liposomes; when positive, a pink line appears. The test has been compared with microscopic examination of thin blood smears and with Quantitative Buffy Coat malaria test (QBC(R) in a single-blind study. A total of 358 patients who had returned to France from malarial areas and consulted their doctor with symptoms or for a routine examination were enrolled in the study; 33 of them were found to have a falciparum malaria infection by the diagnostic test. On the day of consultation, the specificity of the ParaSight(R)-F test was 99% and its sensitivity 94%. The follow-up of infected patients after treatment showed that the test became negative later than the other reference tests. There was no correlation between antigen persistence and the intensity of the ParaSight(R)-F signal or circulating parasitaemia. No cross-reaction was noted for seven malaria cases due to other Plasmodium species. The test was performed quickly (10 tests in 20 minutes), was easy to read, and required minimal space. For cases of imported malaria, the test's specificity and low threshold for detection could make it a valuable adjunct test. However, in its present form, it cannot replace microscopic techniques which are species-specific and quantitative. In endemic areas, the test seems to be very promising by its results and ease of use according to published field studies.

Adolescent↗
PubMed2000

Longitudinal analysis of maternal plasma leptin concentrations during normal pregnancy and pre-eclampsia.

Leptin concentrations have been found to be elevated in cross-sectional studies of established pre-eclampsia. Circulating concentrations of leptin were measured in a cross-sectional study to confirm these findings (19 women with pre-eclampsia and 13 normal pregnant controls) and in a longitudinal study to establish the timing of the increase in leptin concentrations (samples obtained at 16, 20, 24, 28, 32, 36 and 38 weeks gestation from eight women who went on to develop pre-eclampsia and seven normal pregnant controls). In the cross-sectional study, plasma leptin concentrations were significantly greater in women with pre-eclampsia than in normal controls (P: = 0.001). In the longitudinal study, it was found that circulating leptin concentrations rose gradually to 32 weeks and thereafter declined slightly in normals. The concentrations in women destined to develop pre-eclampsia were consistently higher from 20 weeks gestation (P: = 0.04-0.003) and, in contrast to the normal controls, rose markedly from 32 weeks as pre-eclampsia developed. This study confirms that plasma leptin concentrations are increased in established pre-eclampsia and reports for the first time that leptin concentrations are elevated before pre-eclampsia is clinically evident.

Adult↗
PubMed2002

Norepinephrine and vital organ blood flow.

OBJECTIVE: To test whether norepinephrine (NE) infusion at 0.4 microg kg(-1) min(-1) adversely affects regional blood flow in the normal mammalian circulation. DESIGN AND SETTING: Randomized cross-over experimental animal study in a university-affiliated physiology institute. SUBJECTS: Six merino ewes. INTERVENTIONS: Staged insertion of transit-time flow probes around the ascending aorta and circumflex coronary, superior mesenteric and left renal arteries. In conscious animals with chronically embedded flow probes randomization to either 6 h of placebo (saline) or drug (NE at 0.4 microg kg(-1) min(-1)). MEASUREMENTS AND RESULTS: Compared to placebo, NE significantly increased mean arterial pressure (84.4 vs. 103.8 mmHg), heart rate (61.0 vs. 74.6 bpm) and cardiac output (3.76 vs. 4.78 l/min). These changes were associated with an increase in coronary blood flow (24.2 vs. 37.4 ml/min) and renal blood flow (215.2 vs. 282.0 ml/min) but no change in mesenteric blood flow. The increase in renal and coronary blood flow was associated with an increase in regional conductance (regional vasodilatation), while mesenteric conductance fell (mesenteric vasoconstriction). Urine output (91+/-17 vs. 491+/-360 ml/h) and creatinine clearance (61+/-18 vs. 89+/-12 ml/min) increased during NE infusion. CONCLUSIONS: NE infusion does not induce vital organ ischaemia in the normal mammalian circulation. Furthermore, it results in a significant increase in coronary and renal blood flow with a concomitant improvement in urine output and creatinine clearance.

Animals↗
PubMed2005

Effects of intravenous arginine vasopressin on epicardial coronary artery cross sectional area in a swine resuscitation model.

Although arginine vasopressin (AVP) has been shown to be a promising drug during cardiopulmonary resuscitation (CPR), concern has been raised about the potential for AVP-mediated vasoconstriction of the coronary arteries. In a prospective, randomized laboratory investigation employing an established porcine model, the effects of AVP on haemodynamic variables, left anterior descending (LAD) coronary artery cross sectional area employing intravascular ultrasound (IVUS), and return of spontaneous circulation were studied. During sinus rhythm, the LAD coronary artery cross sectional area was measured by IVUS at baseline, and 90 s and 5 min after AVP (0.4 U/kg IV). Following a 60 min recovery, ventricular fibrillation was induced. At 4 min, chest compressions were initiated; AVP (0.4 U/kg IV) was injected at 5.5 min, and defibrillation performed at 8 min. LAD coronary artery cross sectional area was measured by IVUS at the pre-arrest baseline, 90 s after drug injection during CPR, and 5 min after return of spontaneous circulation. Compared with baseline, the mid-LAD coronary artery cross sectional area increased significantly (P<.05) 90 s and 5 min after AVP administration (9.2+/-.5mm2 versus 10.7+/-.6mm2 versus 11.7+/-.6mm2, respectively) during normal sinus rhythm. Similarly during ventricular fibrillation and CPR plus AVP, the mid-LAD coronary artery cross sectional area increased at 90 s after AVP compared with baseline (9.5+/-.6mm2 versus 11.0+/-.7mm2; P<.05). Moreover, the cross sectional area increased further 5 min after return of spontaneous circulation (9.5+/-.6mm2 versus 14.0+/-.8mm2, P<.05). In conclusion, in this experimental model with normal coronary arteries, AVP resulted in significantly increased LAD coronary artery cross sectional area during normal sinus rhythm, during ventricular fibrillation with CPR, and after return of spontaneous circulation.

Anatomy, Cross-Sectional↗
PubMed1997

Functional outcome after the Fontan operation: factors influencing late morbidity.

OBJECTIVES: The purpose of this study was to describe the functional outcome of a large number of patients after modifications of the Fontan operation and to investigate perioperative risk factors that might influence late functional state. METHODS: A comprehensive cross-sectional review of the first 500 patients undergoing a Fontan operation at our institution was undertaken. Those surviving with an intact Fontan circulation were reviewed by questionnaire to assess functional status and medication history. Medical records, chest roentgenograms, echocardiograms, cardiac catheterizations, and laboratory investigations were also reviewed to assess postoperative status. RESULTS: Three hundred sixty-three long-term survivors with an intact Fontan circulation were identified during cross-sectional follow-up. Median age at operation was 5.0 years (range 0.4 to 31 years), and median follow-up was 5.4 years (range 1.7 to 20 years). Most patients (91.1%) were in New York Heart Association class I or II. In a multivariate model, poor (class III or IV) functional state was associated with longer duration of follow-up (p < 0.001), a prior atrial septectomy (p = 0.03), and a prior main pulmonary artery-ascending aorta anastomosis (p = 0.05). CONCLUSIONS: A poor functional outcome is uncommon after the Fontan operation but becomes more frequent with increasing duration of follow-up.

Adolescent↗
PubMedDate not supplied

Effect of long-term ketanserin treatment on 5-HT levels, platelet aggregation and peripheral circulation in patients with Raynaud's phenomenon. A double-blind, placebo-controlled cross-over study.

The long-term effects of the serotonergic (5-hydroxy-tryptamine, 5-HT) receptor antagonist, ketanserin, on 5-HT levels in whole blood, platelet aggregation and peripheral circulation were investigated in a double-blind placebo-controlled cross-over study. In 13 patients with Raynaud's phenomenon, 5-HT and catecholamine levels in whole blood were determined and platelet aggregation assayed after addition of ADP, collagen and 5-HT. Peripheral circulation was evaluated with fingertip temperatures and finger plethysmography before and after local cooling, with measurements repeated after indirect sympathetic blockade by body warming and after alcohol. Patients' symptoms were continuously registered in an individual diary. All measurements were performed 8 to 12 hours after the last drug intake. Five of seven scleroderma patients reported beneficial effects of ketanserin treatment and all six patients with primary Raynaud's phenomenon reported less severe and shorter cold-induced attacks. 5-HT levels in whole blood were significantly reduced after 5 weeks of ketanserin treatment (p less than 0.001) with a tendency for persistence of this reduction after halting of the medication (a "carry-over" effect). Platelet aggregation velocity induced by ADP, collagen and 5-HT was unaffected after ketanserin treatment. The diastolic blood pressure in these patients was decreased from 77.5 mmHg to 71.0 mmHg (p less than 0.001) after ketanserin, but the finger systolic blood pressure (FSBP) was unchanged. After sympathetic blockade by body warming, patients with ketanserin treatment had a paradoxical reduction in both FSBP and finger-tip temperatures, which makes a supposed alpha-receptor-blocking effect of ketanserin less likely. The reduced 5-HT levels in whole blood may explain the subjective favourable effect on patients with Raynaud's phenomenon.

Clinical Trials as Topic↗
PubMedDate not supplied

[New strain-specific determinants in the hemagglutinins of influenza B viruses isolated in 1983-1984].

A comparative study of sensitivity to inhibitors and antigenic composition of hemagglutinins of influenza B virus strains isolated in the epidemic season of 1983-1984 and those circulating in 1940-1981 was carried out. The method of selective adsorption of highly active rabbit and rat sera demonstrated that hemagglutinins of contemporary influenza B viruses had both common cross-reacting determinants with previously circulating variants and qualitatively different, strain-specific ones. Among the variants isolated in 1983-1984, three subgroups of viruses were detected with different strain-specific hemagglutinin determinants.

Adsorption↗