Search PubMed⌕ Search

Biomedical subjects

C Lincoln

Publications and source records attributed to C Lincoln.

At least 37 records · Page 2Linked to original sources
PubMed1999

Antioxidant protection against iron toxicity: plasma changes during cardiopulmonary bypass in neonates, infants, and children.

Cardiopulmonary bypass surgery is associated with the release of low molecular mass iron, which increases the saturation of plasma transferrin to over 50% in all adult patients treated. In a significant minority, however plasma transferrin becomes 100% iron saturated and non-transferrin bound iron can be detected in the plasma. An iron-saturated transferrin is also a common physiological finding in normal term and pre-term infants at a time when their plasma antioxidants, which protect against iron toxicity and radical scavenging, are profoundly different from those seen in adults. This study was conducted to assess the extent to which antioxidants, which protect against iron toxicity, are altered in neonates, infants, and children undergoing cardiopulmonary bypass surgery.

Antioxidants↗
PubMed1999

VEGI, a novel cytokine of the tumor necrosis factor family, is an angiogenesis inhibitor that suppresses the growth of colon carcinomas in vivo.

A novel member of the tumor necrosis factor (TNF) family has been identified from the human umbilical vein endothelial cell cDNA library, named vascular endothelial growth inhibitor (VEGI). The VEGI gene was mapped to human chromosome 9q32. The cDNA for VEGI encodes a protein of 174 amino acid residues with the characteristics of a type II transmembrane protein. Its amino acid sequence is 20-30% identical to other members of the TNF family. Unlike other members of the TNF family, VEGI is expressed predominantly in endothelial cells. Local production of a secreted form of VEGI via gene transfer caused complete suppression of the growth of MC-38 murine colon cancers in syngeneic C57BL/6 mice. Histological examination showed marked reduction of vascularization in MC-38 tumors that expressed soluble but not membrane-bound VEGI or were transfected with control vector. The conditioned media from soluble VEGI-expressing cells showed marked inhibitory effect on in vitro proliferation of adult bovine aortic endothelial cells. Our data suggest that VEGI is a novel angiogenesis inhibitor of the TNF family and functions in part by directly inhibiting endothelial cell proliferation. The results further suggest that VEGI maybe highly valuable toward angiogenesis-based cancer therapy.

Amino Acid Sequence↗
PubMed1998

LIGHT, a novel ligand for lymphotoxin beta receptor and TR2/HVEM induces apoptosis and suppresses in vivo tumor formation via gene transfer.

LIGHT is a new member of tumor necrosis factor (TNF) cytokine family derived from an activated T cell cDNA library. LIGHT mRNA is highly expressed in splenocytes, activated PBL, CD8(+) tumor infiltrating lymphocytes, granulocytes, and monocytes but not in the thymus and the tumor cells examined. Introduction of LIGHT cDNA into MDA-MB-231 human breast carcinoma caused complete tumor suppression in vivo. Histological examination showed marked neutrophil infiltration and necrosis in LIGHT expressing but not in the parental or the Neo-transfected MDA-MB-231 tumors. Interferon gamma (IFNgamma) dramatically enhances LIGHT-mediated apoptosis. LIGHT protein triggers apoptosis of various tumor cells expressing both lymphotoxin beta receptor (LTbetaR) and TR2/HVEM receptors, and its cytotoxicity can be blocked specifically by addition of a LTbetaR-Fc or a TR2/HVEM-Fc fusion protein. However, LIGHT was not cytolytic to the tumor cells that express only the LTbetaR or the TR2/HVEM or hematopoietic cells examined that express only the TR2/HVEM, such as PBL, Jurkat cells, or CD8(+) TIL cells. In contrast, treatment of the activated PBL with LIGHT resulted in release of IFNgamma. Our data suggest that LIGHT triggers distinct biological responses based on the expression patterns of its receptors on the target cells. Thus, LIGHT may play a role in the immune modulation and have a potential value in cancer therapy.

Apoptosis↗
PubMed1998

Left ventricular dysfunction after open repair of simple congenital heart defects in infants and children: quantitation with the use of a conductance catheter immediately after bypass.

OBJECTIVE: Quantification of myocardial injury after the simplest pediatric operations by load-independent indices of left ventricular function, using conductance and Mikro-Tip pressure catheters (Millar Instruments, Inc., Houston, Tex.) inserted through the left ventricular apex. METHODS: Sixteen infants and children with intact ventricular septum undergoing cardiac operations had left ventricular function measured, immediately before and after bypass. Real-time pressure-volume loops were generated by conductance and Mikro-Tip pressure catheters placed in the long-axis via the left ventricular apex, and preload was varied by transient snaring of the inferior vena cava. RESULTS: Good quality pressure-volume loops were generated in 13 patients (atrial septal defects, n = 11; double-chambered right ventricle, n = 1; supravalvular aortic stenosis, n = 1; age 0.25 to 14.4 years, weight 3.1 to 46.4 kg). Their mean bypass time was 41 +/- 14 minutes and mean aortic crossclamp time 27 +/- 11 minutes. End-systolic elastance decreased by 40.7% from 0.34 +/- 0.17 to 0.21 +/- 0.15 mm Hg-1.ml-1.kg-1 (p < 0.001). There were no significant changes in the slope of the stroke work-end-diastolic volume relationship, end-diastolic elastance, time constant of isovolumic relaxation, and normalized values of the maxima and minima of the first derivative of developed left ventricular pressure. CONCLUSION: Load-independent indices of left ventricular function can be derived from left ventricular pressure-volume loops generated by conductance and Mikro-Tip pressure catheters during the perioperative period in infants and children undergoing cardiac operations. Incomplete myocardial protection was demonstrated by a deterioration in systolic function after even short bypass and crossclamp times.

Adolescent↗
PubMed1998

The effect of angiotensin converting enzyme inhibition on myocardial function and blood pressure after coronary artery bypass surgery--a randomised study.

OBJECTIVE: To investigate the effect of 6 weeks' pre-operative treatment with the angiotensin converting enzyme inhibitor, quinapril, on left ventricular function when measured 3 months after coronary artery bypass graft surgery and to examine the safety of such treatment. PATIENTS AND METHODS: Patients (96) [86 males, 10 females; mean age 61 years] with chronic stable angina, on the waiting list for coronary artery bypass graft surgery, underwent measurement of left ventricular function by resting radionuclide ventriculography. Patients were then randomised to quinapril 20 mg once daily or placebo in a double-blind fashion, in addition to existing anti-anginal therapy and this regimen was continued for up to 6 weeks prior to operation. Measurement of left ventricular function was repeated 3 months following surgery, after recommencement of pre-surgery anti-anginal therapy for 1 week. Effects on systemic vascular resistance (SVR) during bypass were calculated from perfusion records and vasoconstrictor use during operation was documented. The safety of the addition of quinapril to the anti-anginal regimen was assessed by measurement of systemic blood pressure (BP) after the first dose of study medication, measurement of intra-operative BP, administration of inotropes and any intra-operative complications. RESULTS: There was no difference between treatment groups in the pre-study left ventricular ejection fraction (mean (S.D.); 54.9 (13.8)% versus 55.6 (13.2)%, quinapril versus placebo, respectively), or 3 months after surgery (58.1 (13.6)%, versus 56.9 (12.6)%, quinapril versus placebo, respectively). Left ventricular ejection fraction 3 months after surgery did not change significantly from pre-treatment in either group (2.8 (10.7)% and 1.5 (10.1)%; quinapril and placebo, respectively). There was no first-dose hypotension (systolic BP < 100 mmHg). The intra-operative BP and the SVR during bypass in the two treatment groups were not significantly different. The ischaemic time (mean = 56 min) and the use of inotropes were the same in both groups and there was no mortality. CONCLUSIONS: Angiotensin converting enzyme inhibitor treatment before coronary artery bypass graft surgery does not have a significant beneficial effect on left ventricular function following coronary artery bypass graft surgery. Angiotensin converting enzyme inhibition, administered in addition to anti-anginal therapy, does not cause first-dose hypotension or increase morbidity or mortality and can safely be used in patients with coronary heart disease prior to coronary artery bypass graft surgery.

Adult↗
PubMed1998

Understanding the topography of the early psychosis pathways. An opportunity to reduce delays in treatment.

BACKGROUND: This study aims to gain an understanding of treatment delays and their nature in initial psychotic episodes. We investigated to whom people turn for help, how long that approach takes and subsequent delays in commencing treatment. METHOD: Qualitative and quantitative methods were combined with interviews of 62 people suffering from first-episode psychoses, aged 16-30 years, who had recently accessed a specialist mental health service in Melbourne, Australia. A modified version of the World Health Organization Encounter Form was analysed in conjunction with other data. RESULTS: Pathways to care and the ways in which they were experienced were highly variable, with 50% of people experiencing psychotic symptoms before approaching any service. The general practitioner played a key role with 50% of people having had GP contact at some point prior to commencing effective treatment. Where an individual's own efforts to seek early help failed, the role of relatives and others was subsequently vital. CONCLUSIONS: Opportunities exist for shortening delays through targeted health promotion activities and professional training. The need is indicated for a multi-layered or topographical strategy to identify and minimise critical barriers on the route to early intervention. Refinement of interview techniques and instruments of measurement are needed to enhance the explanatory power of data collected.

Adolescent↗
PubMed1997

Cardiopulmonary interactions after Fontan operations: augmentation of cardiac output using negative pressure ventilation.

BACKGROUND: The low-output state is the chief cause of morbidity and mortality after Fontan operations. An alternative hemodynamic tool would be a welcome addition for these patients, who are typically resistant to conventional therapeutic measures. METHODS AND RESULTS: The hemodynamic effects of conversion from conventional intermittent positive pressure ventilation (IPPV) to cuirass negative pressure ventilation (NPV) was investigated in nine acute postoperative Fontan patients on the pediatric intensive care unit and nine anesthetized patients undergoing cardiac catheterization in the convalescent phase after Fontan operations. Pulmonary blood flow was measured using the direct Fick method during IPPV and after a brief period of NPV. In one subgroup of patients, pulmonary blood flow was measured again after reinstitution of IPPV, and in a second subgroup, pulmonary blood flow was measured after an extended period of NPV. A brief period of NPV increased pulmonary blood flow from 2.4 to 3.5 L x min(-1) x /m(-2), with a mean increase of 42%. Pulmonary blood flow continued to improve, with a total increase of 54% after an extended period of NPV. Values fell toward baseline after reinstitution of IPPV. Heart rate was unchanged during NPV, and the improvement in pulmonary blood flow was achieved by an increase in stroke volume from 25 mL/m2 to 37 mL/m2. CONCLUSIONS: Through improvement of the stroke volume alone, NPV brought about a marked increase in the pulmonary blood flow and, hence, cardiac output of Fontan patients. An improvement in cardiac output of this order, and by this mechanism, is currently unmatched by any therapeutic alternatives.

Adolescent↗
PubMed1997

Coagulation factor abnormalities after the Fontan procedure and its modifications.

OBJECTIVE: Recently we reported the prevalence of thromboembolism in patients who underwent the Fontan procedure and its modifications. Although hemodynamic factors may well contribute to thromboembolism, recent evidence suggests that coagulation factor abnormalities may also play a role. We therefore set out to investigate the coagulation status in a group of patients who had undergone the Fontan procedure. METHODS: The study population consists of 20 children who had undergone the Fontan procedure and its modifications. They were examined for coagulation factor abnormalities. Concentrations of serum albumin, total protein, and liver enzymes were also measured. The median age at the time of the operation was 6.2 years (17 months to 8 years) with a male/female ratio of 2.3:1. The median time from the Fontan repair was 4.9 years (18 to 76 months). RESULTS: Protein C (p < 0.001), protein S (p < 0.02), and factor VII (p < 0.001) were significantly lower than the normal range. The changes in serum albumin and total protein and factors II, IX, and X were not significant. CONCLUSIONS: It is possible that deficiency in protein C, protein S, and factor VII partly account for the prevalence of thromboembolism after Fontan-type repairs. The risk of long-term anticoagulation should be weighed against the best palliative procedure for these patients. We suggest that reduced protein C, protein S, and factor VII levels in this group of patients should be regarded as risk factors and that such patients should be treated with anticoagulants.

Child↗
PubMed1997

Synovial sarcoma of the heart.

Primary synovial sarcomas of the heart are exceptionally rare tumours, only five being previously documented. We report a sixth case and review published data. Ages ranged from 13-53 (mean 40.8) years. There were four men and two women who characteristically presented with syncope or dyspnoea. Most of the tumours arose in the right atrium where they formed pedunculated or polypoid masses. In the previously documented cases, all patients died within 9 months. However in our case, local excision was felt to have been complete and the patient remains disease free at 10 months.

Adolescent↗
PubMed1997

Anatomical criteria for the diagnosis of sinus venosus defects.

BACKGROUND: The diagnosis of sinus venosus defects remains a matter of debate. It is crucial to provide solid anatomical criteria, by identifying the very nature of the atrial septum relative to sinus venosus defects, to diagnose and differentiate them from other interatrial communications. OBJECTIVE: This study was designed to reestablish the anatomical criteria for the diagnosis of sinus venosus defects. METHODS: Five specimens with sinus venosus defects from the cardiopathological museum were examined. Study of the abnormal hearts was supplemented by examining the extent and structure of the atrial septum in 10 normal hearts. The echocardiograms and surgical notes were reviewed from 18 patients seen between July 1991 and August 1996 at the Royal Brompton Hospital in London diagnosed preoperatively to have a sinus venosus defect. RESULTS: The nature of the oval fossa and its muscular borders were identified in the normal hearts. In all three autopsied specimens of the superior variety of sinus venosus defect, the mouth of the superior caval vein was overriding the intact muscular anterosuperior border of the oval fossa. Two specimens thought initially to have the inferior variety of sinus venosus defect were re-classified as having defects within the oval fossa as it was the deficient oval fossa itself, rather than its intact muscular border, that was overridden by the mouth of the inferior caval vein. Sixteen patients had been diagnosed echocardiographically as exhibiting the superior variant of the defect. Retrospective review showed overriding of the superior caval vein across the upper rim of the oval fossa in 12 patients. These findings were confirmed by surgery in 11 patients with the 12th awaiting operation. Overriding of the fossa by the caval vein was not found in the other four patients. Surgery in all of these showed the defect to be within the oval fossa. In two patients diagnosed echocardiographically as having inferior defects, the surgical findings confirmed a biatrial connection of the inferior caval vein in one patient, the findings in the second were equivocal. CONCLUSIONS: The key anatomical criterion for the diagnosis of sinus venosus defects is overriding of the mouth of the superior or inferior caval vein across the intact muscular border of the oval fossa. The interatrial communication is then formed within the mouth of the overriding vein, and is outside the confines of the oval fossa.

Adolescent↗
PubMed1997

Cardiopulmonary interactions in healthy children and children after simple cardiac surgery: the effects of positive and negative pressure ventilation.

OBJECTIVE: To investigate the effects of cuirass negative pressure ventilation on the cardiac output of a group of anaesthetised children after occlusion of an asymptomatic persistent arterial duct, and a group of paediatric patients in the early postoperative period following cardiopulmonary bypass. DESIGN: Prospective study. SETTING: The paediatric intensive care unit and catheter laboratory of a tertiary care centre. PATIENTS: 16 mechanically ventilated children were studied: seven had undergone surgery for congenital heart disease, and nine cardiac catheterisation for transcatheter occlusion of an isolated asymptomatic persistent arterial duct. INTERVENTIONS: Cardiac output was measured using the direct Fick method during intermittent positive pressure ventilation and again after a short period of negative pressure ventilation. In five of the postoperative patients a third measurement was made following reinstitution of positive pressure ventilation. RESULTS: Negative pressure ventilation was delivered without complication, with no significant change in systemic arterial oxygen and carbon dioxide tension. The mixed venous saturation increased from 74% to 75.8% in the healthy children, and from 58.9% to 62.3% in the postoperative group. Negative pressure ventilation increased the cardiac index from 4.0 to 4.5 l/min/m2 in the healthy children, and from 2.8 to 3.5 l/min/m2 in the surgical group. The increase was significantly higher in the postoperative patients (28.1%) than the healthy children (10.8%). CONCLUSIONS: While offering similar ventilatory efficiency to positive pressure ventilation, cuirass negative pressure ventilation led to a modest improvement in the cardiac output of healthy children, and to a greater increase in postoperative patients. There are important cardiopulmonary interactions in normal children and in children after cardiopulmonary bypass, and by having beneficial effects on these interactions, negative pressure ventilation has haemodynamic advantages over conventional positive pressure ventilation.

Adolescent↗
PubMed1997

Left ventricular parallel conductance during cardiac cycle in children with congenital heart disease.

This study examines the accuracy of the conductance catheter technique and, in particular, parallel conductance [expressed as offset volume (Vc)] changes during the cardiac cycle in the human left ventricle. Two groups of patients were assessed: group 1, with an open atrial septal defect, and group 2, with an interventricular communication. In a subgroup, pre- and postoperative data were compared to assess the possible impact of shunting or anatomic considerations on our measurements. Vc is normally obtained by a saline-dilution technique previously described by Baan et al. [Vc(Baan); J. Baan, E. T. Van der velde, H. G. Debruin, G. J. Smeenk, J. Koops, A. D. Van Dijk, D. Temmerman, P. J. Senden, and B. Buis. Circulation 70: 812-823, 1984]. This does not take into account potential changes during the cardiac cycle. Four cardiac cycles were taken from the hypertonic saline washin and were divided into six equal isochrones between the maximum and minimum first derivatives of left ventricular pressure (dP/dtmax and dP/dtmin, respectively). The apparent ventricular volume was regressed against stroke volume for the corresponding cardiac cycle. The volume at the gamma-intercept corresponds to the Vc at each time interval [Vc(t)]. In group 1, there was a variation in Vc(t) during systole, but the temporal changes were quite small, on the order of 4.28% (SD = 5.18%) of total corrected end-diastolic volume (mean maximal variation of 2.60 ml). Furthermore, the value of Vc obtained at dP/dtmax was not significantly different from that obtained at dP/dtmin. For group 2 as a whole, mean Vc(Baan) did not change significantly with ventricular septal defect closure (preoperative, 8.85 +/- 11.1 ml; postoperative, 9.82 +/- 11.84 ml). Group 2 children also exhibited a systolic cyclical variation in Vc(t) similar to group 1. Finally, Vc(t) as a percentage of end-diastolic volume was no different when group 1 and group 2 were compared. We conclude that in the left ventricle, even in the presence of a left-to-right shunt, there is a small but insignificant difference in parallel conductance during ventricular ejection. The magnitude of this cyclical change does not preclude ventricular volume measurement in congenital heart disease by the conductance catheter technique.

Child↗
PubMed1997

The SAR1 gene of Arabidopsis acts downstream of the AXR1 gene in auxin response.

A screen for suppressors of the auxin resistant mutant axr1 in Arabidopsis thaliana has identified at least three second site suppressor loci called Suppressor of Auxin Resistance (SAR). In this study we focus on the SAR1 gene. Previous studies have documented the effects of the axr1 mutations on auxin-inhibition of root growth, auxin-induced gene expression, seedling morphology and aerial morphology. In this study, we show that the axr1 mutations also affect root hair development and epidermal cell length. The sar1-1 mutation suppresses at least partially, every aspect of the axr1 phenotype. Genetic experiments indicate that this suppression is gene specific. When crossed with the auxin-resistant mutant aux1-7, the suppressor has little affect on auxin response. However, the morphology of sar1-1 aux1-7 inflorescences is different from either of the single mutants indicating that both genes play a role in auxin mediated development of the inflorescence. The sar1-1 mutation also affects morphology in an AXR1 background. sar1-1 plants are shorter than wild-type, have altered leaf morphology, flower earlier than wild-type plants and appear to have reduced cell division in the primary root. In most respects sar1-1 axr1 and sar1 AXR1 plants are indistinguishable, indicating that sar1 both suppresses and is epistatic to axr1. Based on these results, we propose that SAR1 acts after AXR1 and that a major function of AXR1 is to relieve SAR1 mediated repression of auxin response.

Arabidopsis↗
PubMed1996

Relationship between type of outflow tract repair and postoperative right ventricular diastolic physiology in tetralogy of Fallot. Implications for long-term outcome.

BACKGROUND: Restrictive right ventricular (RV) physiology can be present early and late after tetralogy of Fallot repair. It is associated with a complicated early postoperative course but is favorable late after repair because it is associated with less pulmonary regurgitation, better exercise tolerance, and less QRS prolongation and symptomatic ventricular arrhythmias. It is not known, however, whether in the current surgical era, this physiology is present in tetralogy of Fallot patients at mid-term follow-up and whether it is related to the type of RV outflow tract repair. Finally, the impact of this physiology on the early evolution of QRS prolongation has not been examined previously. In this study we attempted to address these issues in a cohort of recently operated patients. METHODS AND RESULTS: Ninety-five patients were studied 4.3 years after repair by Doppler echocardiography, serial electrocardiograms, and chest radiographs. Restrictive RV physiology defined by the presence of antegrade pulmonary artery flow in late diastole was present in 38% of the patients. It was more common in patients with transannular patch (TAP) repair compared with non-TAP repair (50% versus 21%, P < .05). QRS duration at follow-up was 121.2 +/- 17.6 and 132.6 +/- 11.8 ms in restrictive and nonrestrictive patients with TAP repair, respectively (P < .02). CONCLUSIONS: Restrictive RV physiology has been identified at mid-term follow-up in a contemporary surgical series. It is associated with less QRS prolongation, regardless of the technique used for outflow tract repair, and may be associated with fewer long-term complications. Nonrestrictive physiology is associated with the most marked QRS prolongation. This subgroup is most at risk from the late deleterious consequences of chronic pulmonary regurgitation.

Adolescent↗