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PubMed1982

Role of central and peripheral chemoreceptors in diving responses of ducks.

Using techniques of vascular isolation and subsequent perfusion we have investigated the effects of altering blood gas tensions, in the cerebral and carotid body circulations, on some cardiovascular responses to diving in unanesthetized ducks. After denervating the right carotid body, perfusion of the innervated left carotid body with hyperoxic blood significantly reduced diving bradycardia and reduced the increase in hindlimb vascular resistance (HLVR) in 1-min dives compared with dives in which the innervated carotid body was autoperfused. Denervation of systemic arterial baroreceptors reduced the fall in heart rate (HR) and increased the rise in HLVR in all dives. Cross-perfusion of the head, from a donor with blood of normal blood gas tensions, did not significantly affect HR or HLVR in 2-min dives compared with dives in which the head was autoperfused. however, cross-perfusing the cerebral circulation with blood of elevated PaCO2 caused significantly greater increases in HLVR than when high PaCO2 only affected the peripheral circulation. We conclude that peripheral chemoreceptors cause virtually all the bradycardia in the later stages of a dive but only about one-half the increase in HLVR, a significant contribution comes from the stimulation of central chemoreceptors with blood of high PaCO2.

Animals↗
PubMed2002

Magnetic resonance angiography of collateral compensation in asymptomatic and symptomatic internal carotid artery stenosis.

OBJECTIVE: In patients with stenosis of the internal carotid artery (ICA), the presence of collateral circulatory pathways may be crucial to maintain cerebral perfusion pressure, metabolism, and function. The purpose of the present study was to determine whether patients with asymptomatic stenosis of the ICA have a better collateral ability of the circle of Willis when compared with patients with symptomatic ICA stenosis. METHOD: Magnetic resonance angiography consisting of the circle of Willis was performed in 19 patients with severe asymptomatic ICA stenosis and in 21 patients with severe symptomatic ICA stenosis prior to carotid endarterectomy and in 53 control subjects. Between group comparisons were made for function (directional flow) and anatomy (diameter). RESULTS: In patients with asymptomatic ICA stenosis, the prevalence of collateral flow via the anterior communicating artery was significantly increased (37%, 7 of 19) compared with symptomatic patients (10%, 2 of 21) and control subjects (0%; P <.001). Patients with asymptomatic ICA stenosis demonstrated the largest mean diameter of the anterior communicating artery (1.33 +/- 0.18 mm) compared with patients with symptomatic ICA stenosis (1.22 +/- 0.18 mm) and control subjects (1.06 +/- 0.10 mm, P <.05). No differences in collateral flow pattern or diameter were found for the posterior communicating artery between the groups. CONCLUSIONS: The present cross-sectional study demonstrates the importance of an adequate hemodynamic compensation via the circle of Willis in patients with ICA stenosis. Whether differences in collateral compensation can be used to select patients for CEA has yet to be determined.

Aged↗
PubMed2002

Regional cerebral blood flow in cats with cross-linked hemoglobin transfusion during focal cerebral ischemia.

The beneficial effect of hemodilution on cerebral blood flow (CBF) during focal cerebral ischemia is mitigated by reduced arterial oxygen content (CaO2). In anesthetized cats subjected to permanent middle cerebral artery occlusion, the time course of regional CBF was evaluated after isovolemic exchange transfusion with either albumin or a tetrameric hemoglobin-based oxygen carrier. The transfusion started 30 min after arterial occlusion. We tested the hypothesis that bulk oxygen transport (CBF x CaO2) to ischemic tissue is increased by hemoglobin transfusion at a hematocrit of 18% compared with albumin-transfused cats at a hematocrit of 18% or control cats at a hematocrit of 30% and equivalent arterial pressure. In the nonischemic hemisphere, CBF increased selectively after albumin transfusion, and oxygen transport was similar among groups. In the ischemic cortex, albumin transfusion increased CBF, but oxygen transport was not increased above that of the control group. Hemoglobin transfusion increased both CBF and oxygen transport in the ischemic cortex above values in the control group, but the increase was delayed until 4 h of ischemia. Consequently, acute injury volume measured at 6 h of ischemia was not significantly attenuated. In contrast to the cortex, CBF in the ischemic caudate nucleus was not substantially increased by either albumin or hemoglobin transfusion. Therefore, in a large animal model of permanent focal ischemia in which transfusion starts 30 min after ischemia, tetrameric cross-linked hemoglobin transfusion can augment oxygen transport to the ischemic cortex, but the increase can be delayed and not necessarily provide protection. Moreover, an end-artery region such as the caudate nucleus is less likely to benefit from hemodilution.

Animals↗
PubMed1995

A cross-sectional study of catheter-related thrombosis in children receiving total parenteral nutrition at home.

We performed a cross-sectional evaluation of deep vein thrombosis (DVT) related to the use of central venous lines (CVLs) in all pediatric patients receiving home total parenteral nutrition at our institution (N = 12). All children (5 months to 17 years of age) were examined with bilateral upper limb venography. All CVLs were flushed daily with heparin (200 units). At the time of evaluation, 49 CVLs had been placed in the 12 children. Of the 39 CVLs removed, 27 (66%) were blocked; venograms had not been previously obtained except of one child. Eight children had clinical evidence of superficial collateral circulation in the upper portion of the chest and the upper extremities; five had intermittent symptoms of superior vena cava obstruction. On venography, 8 of the 12 children had extensive evidence of DVT; two were unilateral and six bilateral. Five children were treated with warfarin (0.12 to 0.28 mg/kg per day) to achieve an international normalized ratio of 1.4 to 1.8. Neither bleeding nor further CVL-related DVT has occurred. We conclude that the risk of CVL-related DVT in children requiring home total parenteral nutrition is high, and that venography should be performed early in the event of CVL blockage. A multicenter, controlled trial assessing optimal warfarin therapy in this patient population is indicated.

Adolescent↗
PubMed1995

A blind, randomized comparison of the circulatory effects of dopamine and epinephrine infusions in the newborn piglet during normoxia and hypoxia.

OBJECTIVE: To determine the hemodynamic responses to dopamine and epinephrine infusions in newborn piglets during normoxia and hypoxia. DESIGN: Prospective, randomized, blind cross-over study. SUBJECTS: Newborn piglets (n = 7). INTERVENTIONS: Animals were acutely instrumented for measurements of cardiac output, pulmonary and systemic pressures, carotid and coronary artery blood flow, and coronary artery oxygen consumption. Dopamine at infusion rates of 2 to 16 micrograms/kg/min and epinephrine 0.2 to 1.6 micrograms/kg/min were administered during normoxia. Six piglets were similarly prepared and were then made hypoxic to an arterial O2 saturation of 45% to 50%. Epinephrine at infusion rates of 0.2 to 3.2 micrograms/kg/min and dopamine at rates of 2 to 32 micrograms/kg/min were administered in random order during hypoxia. MEASUREMENTS AND MAIN RESULTS: During normoxia, cardiac output increased similarly with both drugs and was significantly increased by > or = 0.2 micrograms/kg/min of epinephrine and significantly increased by 8 or 16 micrograms/kg/min of dopamine. Mean arterial blood pressure was not affected by dopamine but was significantly increased by epinephrine at a rate of 1.6 micrograms/kg/min. The relative effects of the drugs on pulmonary and systemic vascular resistance differed, the pulmonary/systemic vascular resistance ratio was reduced at the higher doses of epinephrine (i.e., 0.8 and 1.6 micrograms/kg/min) and was unaffected by dopamine. Coronary artery oxygen consumption and coronary blood flow increased significantly with both medications at rates > 0.4 and 4 micrograms/kg/min, respectively. Increases of both variables were greater with epinephrine than with dopamine. Myocardial extraction ratio was unaffected by dopamine and reduced at 0.2 and 1.6 micrograms/kg/min of epinephrine. Hypoxia caused significant increases in cardiac index, systemic blood pressure, pulmonary arterial pressure, carotid artery blood flow, coronary artery blood flow, coronary oxygen consumption, coronary oxygen extraction ratio, and the pulmonary/systemic vascular resistance ratio. Mean systemic arterial blood pressure increased significantly with 1.6 and 3.2 micrograms/kg/min of epinephrine, but was not significantly affected by dopamine at any infusion rate. Cardiac index was not affected significantly by either of the medications. Thus, there was a significant increase in the calculated systemic vascular resistance index with the highest dose of epinephrine, in contrast to the slight, statistically significant, decrease in calculated systemic vascular resistance index with the highest dose of dopamine. Epinephrine significantly reduced pulmonary arterial pressures at 0.2, 0.4, and 0.8 microgram/kg/min. Dopamine had no effect on this variable. The pulmonary/systemic vascular resistance ratio was significantly reduced by epinephrine at doses of 0.2 and 3.2 micrograms/kg/min, whereas the highest dose of dopamine caused a significant increase in the pulmonary/systemic vascular resistance ratio. CONCLUSIONS: Epinephrine infusion during normoxia increases systemic pressure more than pulmonary arterial pressure at doses > or = 8 micrograms/kg/min, and furthermore, produces a more appropriate hemodynamic profile in the presence of hypoxic pulmonary hypertension than dopamine infusion, in the acutely operated anesthetized piglet.

Animals↗
PubMed1987

Physiologic regulation and pathologic disorders of fibrinolysis.

Physiologic fibrinolysis is a reparative process that occurs in response to hemostatic plug or thrombus formation. The final enzymatic step, fibrin proteolysis, results from a coordinated interaction of enzymes and inhibitors, which produces effective action at the site of the disease and spares the proteins of the blood or uninvolved parts of the vascular system. The agent of fibrinolysis, the enzyme plasmin, is derived from its zymogen (plasminogen) through limited proteolysis effected by plasminogen activators. They can be grouped according to functional and immunologic properties into the tissue type and urokinase-like plasminogen activators. The ability of alpha 2 antiplasmin to neutralize efficiently free (nonfibrin-bound) plasmin prevents inappropriate systemic activation of fibrinolysis. This control is superseded in certain conditions, such as with the therapeutic administration of plasminogen activators to lyse pathologic thrombi, when plasmin degrades plasma fibrinogen into degradation fragments (X, Y, D, and E). Degradation of cross-linked fibrin results in distinctive products that are characterized by cross-linked (factor XIIIa-induced) derivatives such as D dimer. Disease states resulting from abnormalities in the fibrinolytic system include both hemorrhagic disorders, resulting from excessive fibrinolysis, and thrombosis, as the result of deficient fibrinolysis. Hyperfibrinolysis can result from pharmacologic administration of activators or from defective inhibition produced by alpha 2 antiplasmin deficiency. Hypofibrinolytic thrombosis can result from hereditary defects, for instance of plasminogen or fibrinogen, or from pharmacologic inhibition of fibrinolysis such as with epsilon aminocaproic acid. Laboratory evaluation of fibrinolysis is useful for monitoring fibrinolytic therapy and assessing thrombotic disorders and bleeding; it also includes the specific measurements of plasminogen activator, plasminogen, plasmin, inhibitors and circulating fibrinogen, and cross-linked fibrin degradation products.

Fibrin Fibrinogen Degradation Products↗
PubMed2006

Molecular mechanisms involved in T cell migration across the blood-brain barrier.

In the healthy individuum lymphocyte traffic into the central nervous system (CNS) is very low and tightly controlled by the highly specialized blood-brain barrier (BBB). In contrast, under inflammatory conditions of the CNS such as in multiple sclerosis or in its animal model experimental autoimmune encephalomyelitis (EAE) circulating lymphocytes and monocytes/macrophages readily cross the BBB and gain access to the CNS leading to edema, inflammation and demyelination. Interaction of circulating leukocytes with the endothelium of the blood-spinal cord and blood-brain barrier therefore is a critical step in the pathogenesis of inflammatory diseases of the CNS. Leukocyte/endothelial interactions are mediated by adhesion molecules and chemokines and their respective chemokine receptors. We have developed a novel spinal cord window preparation, which enables us to directly visualize CNS white matter microcirculation by intravital fluorescence videomicroscopy. Applying this technique of intravital fluorescence videomicroscopy we could provide direct in vivo evidence that encephalitogenic T cell blasts interact with the spinal cord white matter microvasculature without rolling and that alpha4-integrin mediates the G-protein independent capture and subsequently the G-protein dependent adhesion strengthening of T cell blasts to microvascular VCAM-1. LFA-1 was found to neither mediate the G-protein independent capture nor the G- protein dependent initial adhesion strengthening of encephalitogenic T cell blasts within spinal cord microvessel, but was rather involved in T cell extravasation across the vascular wall into the spinal cord parenchyme. Our observation that G-protein mediated signalling is required to promote adhesion strengthening of encephalitogenic T cells on BBB endothelium in vivo suggested the involvement of chemokines in this process. We found functional expression of the lymphoid chemokines CCL19/ELC and CCL21/SLC in CNS venules surrounded by inflammatory cells in brain and spinal cord sections of mice afflicted with EAE suggesting that the lymphoid chemokines CCL19 and CCL21 besides regulating lymphocyte homing to secondary lymphoid tissue might be involved in T lymphocyte migration into the immuneprivileged CNS during immunosurveillance and chronic inflammation. Here, I summarize our current knowledge on the sequence of traffic signals involved in T lymphocyte recruitment across the healthy and inflamed blood-brain and blood-spinal cord barrier based on our in vitro and in vivo investigations.

Animals↗
PubMed2000

[S-(+)-ketamine versus ketamine racemic mixture: hemodynamic studies].

OBJECTIVE: Evaluation of hemodynamic effects of S-(+)-ketamine versus ketamine-racemic mixture during induction of anesthesia, during steady-state of a fentanyl-midazolam-anesthesia and in the period of aortic cross-clamping during extracorporeal circulation. METHODS PATIENTS: 80 patients scheduled for coronary revascularization. STUDY DESIGN: double-blind, randomized. STUDY 1: Induction of anesthesia with ketamine-racemic mixture (3 mg/kg) or S-(+)-ketamine (1.5 mg/kg) plus midazolam 0.15 mg/kg. PARAMETERS: invasive hemodynamic monitoring including right ventricular volumes and pressure. STUDY 2: Bolus of ketamine-racemic mixture (3 mg/kg), S-(+)-ketamine (1.5 mg/kg) or placebo during steady-state anesthesia with fentanyl and midazolam. PARAMETERS: see study 1, additionally left ventricular systolic and end-diastolic pressure and maximum speed of left ventricular pressure increase (dp/dt). STUDY 3: Bolus of ketamine-racemic mixture (3 mg/kg), S-(+)-ketamine (1.5 mg/kg) or placebo in the period of aortic cross clamping during ECC. PARAMETERS: mean systemic pressure, central venous pressure, reservoir volume. RESULTS STUDY 1: Heart rate and systemic blond pressure remained unchanged until intubation, which caused significant increases of these parameters. Stroke volume Index and cardiac index decreased in the S-(+)-group compared with racemic mixture, right- and left ventricular filling parameters remained unchanged throughout the study. STUDY 2: There were no significant hemodynamic changes with time or between the groups. STUDY 3: Significant arterial vasodilation was observed in the racemic mixture group, venous parameters remained unchanged. CONCLUSION: There were no major differences in the hemodynamic profiles of S-(+)-ketamine and the racemic mixture. S(+)-ketamine did not provide hemodynamic advantages. The use of both preparations should be limited to selected clinical situations in patients with reduced coronary reserve.

Aged↗
PubMed1991

Brain and atrial natriuretic peptides bind to common receptors in brain capillary endothelial cells.

The recent discovery of brain natriuretic peptides (BNP) that stimulates natriuresis, diuresis, and vascular smooth muscle relaxation in a manner similar to that of atrial natriuretic peptide (ANP) suggests the possibility that these endocrine hormones function via some common mechanism. Indirect evidence from several laboratories suggests that BNP and ANP may bind to the same receptors. We examined whether ANP and BNP bind to a common set of receptors in cultured bovine brain capillary endothelial cells and in bovine aortic endothelial cells. Scatchard plot analysis of binding data shows a similar dissociation constant (KD) of approximately 0.3 nM and a maximal binding capacity (Bmax) of 50 fmol/mg protein for both natriuretic peptides in brain capillary cells and 0.6 nM and 80 fmol/mg protein, respectively, in the aortic endothelial cells. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the affinity cross-linked receptor-ligand complex shows a strongly labeled 65-kDa receptor and a 125-kDa band that is likely to be a receptor of the guanylate cyclase type. ANP and BNP cross compete equally for binding to the two receptors identified on the gels. ANP and BNP also stimulate guanosine 3', 5'-cyclic monophosphate production in these cells, consistent with the presence of a functional guanylate cyclase-linked B receptor. We conclude that ANP and BNP share common receptors in brain capillary and aortic endothelial cells.

Animals↗
PubMed2005

Detection and molecular characterisation of group a rotavirus from children in northern Botswana.

OBJECTIVES: To determine the presence of group A rotavirus in human stool samples in northern Botswana and to characterise the circulating strains. DESIGN: A cross sectional study. SETTING: The University of Botswana and Botswana-Havard Partnership for HIV Research. SUBJECTS: A total of 210 stool samples was collected; 104 from hospitalised and 106 from non-hospitalised children, five years and below suffering from gastroenteritis. RESULTS: Out of 210 diarrhoea stool samples collected, 27 (13%) tested positive for group A rotavirus. There was a higher prevalence of infection in hospitalised children (63%) as compared to the non-hospitalised ones (37%). Most rotavirus infections occurred in the age 24 months and below. Of the 13 samples which were positive by PAGE, the predominant electrophoretic pattern detected was the short (S) electrophoretype 9/13 (69%) followed by the long (L) electrophoretype 4/13 (31%). The following G types were detected; G2 (17%), G3 (22%), mixed infections found were G1+G2 (5.6%), G1+G8 (22%), G3+G9 (27.8%) and G1+G3+G9 (5.6%). P[6] was the only VP 4 genotype detected. Rotavirus strains G3P[6] and G3+G9P[6] were identified as the circulating strains in north Botswana. CONCLUSION: The detection of uncommon rotavirus strains and the high proportion of mixed infections suggest a greater diversity of rotavirus infections among children in Botswana than previously reported. Our study reveals a complex epidemiological profile of rotavirus infection in Botswana that may require further molecular characterisation.

Botswana↗
PubMed1997

Lack of effect of short-term lisinopril administration on left ventricular filling dynamics in hypertensive patients with diastolic dysfunction.

Arterial hypertension may be associated with altered left ventricular filling dynamics. The specific goal of this study was to evaluate whether short-term administration of the ACE inhibitor lisinopril in hypertensive patients with an altered diastolic pattern induced an improvement of left ventricular dynamics, assessed by the echocardio-Doppler technique, independently of effects on left ventricular mass. In a double-blind cross-over study 39 essential hypertensive patients with a ratio of peak early to peak atrial velocity (E/A) < 1 were randomized, after a run-in period of 2 weeks without any antihypertensive treatment, to receive lisinopril (20 mg once a day) and placebo for 4 weeks, respectively. At the end of both the run-in and the treatment periods, blood pressure and heart rate were measured and an echocardio-Doppler examination was carried out. The echocardio-Doppler evaluation was performed both at rest and at the peak of a hand-grip test (3 min at 30% of maximal strength). Left ventricular dimensions were obtained from two-dimensionally guided M-mode tracings using the criteria of the American Society of Echocardiography. Left ventricular peak filling rates and filling rate integrals were measured by a pulsed Doppler technique. Lisinopril caused a significant reduction in systolic and diastolic blood pressure at rest (-13/-9 mmHg vs baseline values, p < 0.05; -6/-4 mmHg vs placebo values, p < 0.05) and during isometric exercise (-17/-9 mmHg vs baseline period, p < 0.05; -6/-5 mmHg vs placebo, p < 0.05). Lisinopril did not induce any significant change in left ventricular structure and systolic function. All the left ventricular filling parameters considered (E velocity, A velocity, E/A ratio) both at rest and during isometric exercise did not significantly differ after lisinopril treatment when compared to those obtained in basal conditions and after placebo administration. This double-blind cross-over study demonstrates that short-term afterload reduction induced by lisinopril does not modify altered diastolic dynamics in hypertensive patients. Diastolic dysfunction of the left ventricle is a complex process influenced by a number of functional and structural factors and apparently cannot be significantly improved by short-term blood pressure reduction by antihypertensive therapy.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2006

[Mortality and morbidity in HIV-infected patients undergoing coronary artery bypass surgery: a case control study].

The use of highly active antiretroviral therapy (HAART) in patients with HIV infection has improved survival. This improvement combined with the metabolic effects of treatment has increased cardiovascular risk and the need for cardiac surgery in these patients. We compared morbidity and mortality in HIV-infected patients (cases, n=7) and non-HIV-infected patients (controls, n=21) who underwent isolated coronary artery surgery between 1997 and 2004. The durations of extracorporeal circulation and aortic cross-clamping were shorter in HIV-infected patients (P=.002 and P=.014, respectively). The percentage of patients who experienced complications was similar, at 57.1% in both groups, but there was a slightly higher number of complications per patient in non-HIV-infected individuals. The mean length of total hospitalization was greater in HIV-infected patients (27.1 [13.3] versus 8.8 [5.3] days; P=.003), as was that of postoperative hospitalization (18.2 [15.4] vs 7.9 [4.2] days; P=.08). No HIV-infected patient died or needed a repeat cardiac operation. No progression of the HIV infection was observed. Isolated coronary artery surgery in HIV-infected patients produces good results, and there is no increase in morbidity or mortality. Extracorporeal circulation did not influence disease progression.

Adult↗
PubMed2005

Acute regulation of circulating parathyroid hormone (PTH) molecular forms by calcium: utility of PTH fragments/PTH(1-84) ratios derived from three generations of PTH assays.

CONTEXT: The quantitative evaluation of circulating PTH peaks revealed by PTH assays after HPLC separation constitutes the best way to study the behavior of PTH molecular forms, but it is also impractical. OBJECTIVE: The objective of the study was to investigate the regulation of circulating PTH molecular forms by calcium through the use of PTH fragments/PTH (1-84) ratios derived from PTH assays with different specificities before and after HPLC separation of circulating PTH. DESIGN: CaCl2 and Na citrate were infused in eight volunteers. PTH was measured in serum and HPLC fractions at different calcium concentrations in PTH assays reacting with regions 1-2 (CA), 12-18 (T), and 65-69 (C) of the PTH structure. RESULTS: From hypo- to hypercalcemia, the C/CA ratio had the highest range (1.92 to 9.75; P < 0.001), and the C/T ratio had a higher range (1.69 to 6.11; P < 0.01) than the T/CA ratio (1.15 to 1.86). Human (h) PTH (1-84) represented 32.7 and 4.3% of circulating PTH in hypo- and hypercalcemic HPLC profiles, respectively. These numbers were 5 and 0.9% for amino-terminal (N)-PTH, an amino-terminal form of PTH distinct from hPTH (1-84), 7.3 and 6.8% for non-(1-84) PTH or large C-PTH fragments with a partially preserved N structure, and 54.9 and 88.1% for C-PTH fragments missing a N structure. The HPLC C-PTH fragments to hPTH (1-84) ratio had the most extensive range (1.67 to 20.58). Despite their quantitative differences, all ratios identified identical behavior of PTH fragments relative to PTH (1-84). CONCLUSIONS: PTH assay ratios are an adequate tool to investigate the modulation of PTH molecular forms, even if all PTH assays show some undesirable cross-reactivity with certain circulating forms of PTH.

Adult↗
PubMed1996

The effect of suxamethonium on intracranial pressure and cerebral perfusion pressure in patients with severe head injuries following blunt trauma.

Eleven adult patients with severe head injuries caused by blunt trauma, (Glasgow Coma Score of eight or less after resuscitation), were studied while being mechanically ventilated and sedated in the intensive care unit (ICU). In a double blind randomized cross over trial each patient received a bolus of suxamethonium (1 mg kg-1) or an equal volume of saline (0.02 mL kg-1) before planned physiotherapy. Intracranial pressure (ICP) and mean arterial pressure (MAP) were measured continuously for 10 min after each injection. There were no significant changes in intracranial pressure or cerebral perfusion pressure (CPP) following the administration of suxamethonium or saline. Suxamethonium appears to be a safe drug to use on sedated persons with severe head injuries following blunt trauma.

Adolescent↗
PubMed1986

Species cross-reactivity of anti-LSP antibodies in acute viral hepatitis.

Previous reports have suggested that circulating antibodies reacting with species cross-reactive determinants in the liver-specific membrane lipoprotein (LSP) complex are rare in acute viral hepatitis (AVH) and that their high frequency in chronic active hepatitis (CAH) indicates a fundamental change in antigen specificity of anti-LSP autoantibodies associated with progression to chronic liver disease. In the present study, sera from 20 patients with uncomplicated AVH (10 with virus A and 10 with virus B infection) were examined by radioimmunoassay for antibodies reacting with human, rabbit and rat LSP. All 20 patients were found to be seropositive for antibodies against all 3 LSP preparations. Titres of anti-human and anti-rat LSP were significantly higher (p less than 0.001) than those of anti-rabbit LSP but a strong linear correlation (p less than 0.005) was found between titres of antibodies against the 3 LSP preparations. Cross-inhibition experiments with sera from 10 patients (5 with AVH-A and 5 with AVH-B) failed to reveal any major differences in antigen specificity between anti-rabbit and anti-rat LSP in 8 but results with the remaining 2 patients suggested that their anti-LSP antibodies were not reacting with the same antigens in the 2 LSP preparations. The results indicate that antibodies reacting with species cross-reactive LSP determinants are a normal occurrence in AVH and suggest that, if anti-LSP antibodies are involved in progression to (and/or development of) CAH, this is more likely to be related to a defect in the control of autoreactivity than to inherent differences in target antigen specificities of these autoantibodies in acute and chronic liver diseases, although the latter possibility cannot be totally excluded.

Animals↗
PubMed2000

The significance of the cerebral collateral capacity in patients with carotid atheroma.

OBJECTIVES: to identify the echodensity, stenosis of carotid plaques and cerebral collateral capacity that were associated with various ipsilateral presentations (retinal, cerebrovascular, asymptomatic). DESIGN: cross-sectional study. MATERIALS: forty-four patients, with 44 plaques associated with various presentations, were studied. METHODS: the duplex images of the plaques were analysed echomorphologically in a computer by means of Grey Scale Median (GSM) [hypoechoic (low GSM), hyperechoic (high GSM)]. The percentage (%) reduction of the mean velocity in the middle cerebral artery (PRMCA) on transcranial Doppler, during clamping in carotid endarterectomy, was evaluated to distinguish the competent cerebral collateral supply (low PRMCA) from the non-competent one (high PRMCA). RESULTS: the retinal symptoms were associated with plaques of low median GSM (0), severe median stenosis (90%) and low median PRMCA (0.31) as contrasted with the cerebrovascular symptoms (17, 84%, 0.47, respectively) and asymptomatic status (32, 83%, 0.4, respectively) [(p =0.038 (GSM), p =0.67 (stenosis), p=0.15 (PRMCA)]. The retinal and the cerebrovascular symptoms were distinct in terms of PRMCA (p=0.045). CONCLUSIONS: the retinal symptoms were produced by hypoechoic and possibly embologenic plaques, whereas the cerebrovascular ones possibly by the combination of carotid embolism and a non-competent cerebral collateral circulation. Asymptomatic status was associated with the absence of any relevant mechanism.

Adult↗
PubMed1998

Thromboxane and prostacyclin in maternal and fetal circulation in pre-eclampsia.

OBJECTIVES: A major pathophysiologic change of pre-eclampsia has been attributed to the overproduction of thromboxane A2 (TXA2) mainly from activated platelets. On the other hand, increased biosynthesis of TXA2 has also been reported from preeclamptic placentas. The systemic role of these different sources of TXA2 has not been clarified. The purpose of this study is to define the changes of TXA2 and the antagonizing prostacyclin (PC) in maternal and fetal circulations. METHODS: The stable metabolites of TXA2 and PC [Thromboxine B2 (TXB2) and 6-keto-prostaglandin F1alpha (6-keto-PGF1alpha), respectively] in the cord and maternal blood of nine patients with pre-eclampsia and nine normal parturients were measured by radioimmunoassay. RESULT: In normal pregnancy, the cord blood contained much higher TXB2 (1697+/-898 vs. 267+/-128 ng/ml, P < 0.01) and 6-keto-PGF1alpha (266+/-263 vs. 12.5+/-3.9 ng/ml, P < 0.05) levels than the maternal blood. In the preeclamptic state, a marked increase of TXB2 was noted in both maternal and cord blood, reaching levels which were significantly higher than during normal pregnancy (2995+/-1103 vs. 267+/-128 ng/ml in maternal blood, P < 0.0001, and 3197+/-1288 vs. 1697+/-898 ng/ml in cord blood, P < 0.005). A less significant increase in 6-keto-PGF1alpha (134+/-10.8 vs. 12.5+/-3.9 ng/ml, P < 0.05) was also noted in the maternal blood. Moreover, the level of TXB2 correlated with the diastolic blood pressure of preeclamptic patients before and after delivery. CONCLUSION: The results suggest an abundant source of eicosanoids in the feto-placental circulation, which does not readily cross the placental barrier. In pregnancy complicated with pre-eclampsia, thromboxane level of both fetal and maternal circulations are markedly increased, which may be responsible for the pathophysiologic changes. The lack of adverse systemic effects on the fetus highlights a placental source of TXA2 of transient bioactivity which is rapidly hydrolyzed to non-active TXB2. Federation of Gynecology and Obstetrics

Adult↗