Biomedical subjects

C Bull

Publications and source records attributed to C Bull.

At least 19 recordsLinked to original sources

PubMed1998

Integrated multimodality therapy for embryonal rhabdomyosarcoma of the lower genital tract in postpubertal females.

Embryonal rhabdomyosarcoma of the female lower genital tract is generally regarded as a neoplasm occurring in childhood, but has also been reported in adults. The philosophy of therapy, largely based on data obtained from pediatric patients, has evolved slowly from ultraradical surgery, without adjuvant therapy, to neoadjuvant chemotherapy followed by less radical surgery and postoperative radiation. We report here three cases of lower genital tract rhabdomyosarcoma in postpubertal females. A failure to observe complete responses from any single treatment modality suggests that for embryonal rhabdomyosarcoma in adult and adolescent women a multimodality approach to therapy is essential.

Adolescent↗

PubMed1998

Fate of subpulmonary homograft conduits: determinants of late homograft failure.

PATIENTS AND METHODS: Between 1971 and 1993, 656 conduits were placed in the subpulmonary position. Patients receiving heterografts or valveless conduits and patients dying within 90 days of insertion were excluded; thus 405 homograft conduits were studied. There were 293 aortic homografts, 94 pulmonary, and 18 of unknown type. The end point of conduit failure was defined by conduit replacement for whatever reason, balloon dilation of the conduit, or death of the patient with the conduit in place. The following factors were analyzed: aortic versus pulmonary homograft, antibiotic preservation versus cryopreservation, ABO and Rh compatibility, type of material used for conduit extension, age at operation, size of the conduit, diagnosis, and reoperations. Conduit number (1 to 405) in the series was included in the multivariable model. RESULTS: First conduits and conduits inserted earlier in the series appeared to last longer than second and subsequent conduits and those inserted later in the series (p = 0.001 and 0.003, respectively). Overall survival of conduits at 5, 10, and 15 years was 84% (95% CL, 80% to 88%), 58% (95% CL, 50% to 66%), and 31% (95% CL, 19% to 43%). Corresponding figures for the first conduits were 88% (95% CL, 84% to 92%), 65% (95% CL, 56% to 73%), and 34% (95% CL, 20% to 47%). The longest surviving homograft conduit in our series lasted 22.7 years. Regarded univariately, reoperation (redo worse), order number (recent worse), type of conduit (pulmonary worse than aortic), preservation (cryopreserved worse than antibiotic preserved), and age at operation (older patients worse) were statistically significant. However, in multivariable analysis, including all the above in the model, only reoperation and order number had significant predictive power. When patient survival was considered, patients operated on more recently survived longer despite the fact that their conduits were being replaced earlier. Overall, survival of patients at 5 and 15 years was 95% (95% CL, 93% to 98%) and 85% (95% CL, 77% to 92%), respectively. CONCLUSIONS: Pulmonary and aortic homografts, both cryopreserved and preserved in nutrient antibiotic solution, give similar results. All conduits will probably have to be replaced during the lifetime of the patient. In view of the worse performance of replacement conduits, techniques of repair that avoid the use of conduits should be further explored. Despite gradual deterioration of homograft conduits, they remain an important tool in the correction of many complex lesions with excellent 15-year patient survival.

Adolescent↗

PubMed1998

A murine skeletal muscle ischemia-reperfusion injury model: differential pathology in BALB/c and DBA/2N mice.

Ischemia-reperfusion injuries can occur with diseases such as myocardial infarction and stroke and during surgical procedures such as organ transplantation and correction of aortic aneurysms. We developed a murine model to mimic abdominal aortic aneurysm repair with cross-clamping of the aorta distal to the renal artery. After model development, we compared the normal complement BALB/c mouse with the C5-deficient DBA/2N mouse. To assess quantitative differences, we measured neuromuscular function up to 72 h after ischemia with a subjective clinical scoring system, as well as plasma chemistries, hematology, and histopathology. There were significant increases in clinical scores and creatine phosphokinase, lactate dehydrogenase, and muscle histopathology scores in BALB/c mice compared with those in DBA/2N mice and sham-surgery mice. Muscle histopathology scores of the cranial tibialis and quadriceps correlated well with clinical signs, creatine phosphokinase, and lactate dehydrogenase, and indicated the greatest pathology in these muscle groups. We developed a murine model of skeletal muscle ischemia-reperfusion injury that can utilize the benefits of murine genetic and transgenic models to assess therapeutic principles of this model. Additionally, we have shown a significant reduction in clinical signs, plasma muscle enzyme concentrations, and muscle pathology in the C5-deficient DBA/2N mouse in this model.

Animals↗

PubMed1997

Anthracycline dose in childhood acute lymphoblastic leukemia: issues of early survival versus late cardiotoxicity.

PURPOSE: Late abnormalities of left ventricular (LV) performance occur in most survivors of childhood acute lymphoblastic leukemia (ALL) treated with moderate anthracycline doses. We studied the prevalence of late cardiotoxicity in patients treated with lower anthracycline doses and related this to survival. PATIENTS AND METHODS: Echocardiograms were performed in 50 normal children and 120 relapse-free ALL survivors 6.2 +/- 2.0 years after the end of cumulative daunorubicin doses of 90 mg/m2 (n = 40), 180 mg/m2 (n = 40), or 270 mg/m2 (n = 40) on UKALL X pilot (1982 to 1984) or UKALL X (1985 to 1989) protocols. Age at treatment onset was 4.7 +/- 2.8 years. Cardiac abnormalities were reviewed in light of the UKALL X 5-year disease-free survival rates of 57% (95% confidence interval [CI], 51% to 63%), 61% to 62% (95% CI, 56% to 68%), and 71% (95% CI, 66% to 76%) for the groups that received 90, 180, and 270 mg/m2 of daunorubicin, respectively. RESULTS: ALL survivors had reduced LV fractional shortening (FS) compared with normal (32.3% +/- 4.4% v 35.9% +/- 4.2%, P < .005), which was accounted for by increased LV end-systolic stress (49.4 +/- 13.5 v 42.2 +/- 9.1 g/cm2, P < .001), whereas LV contractility independent of loading conditions was normal for the group as a whole. Of 27 patients (23%) with cardiac abnormalities, 25 (21%) had increased end-systolic stress, whereas only two (2%) had reduced contractility. The proportion with cardiac abnormality was similar in the three dose groups. Anthracycline dose, age at treatment, sex, follow-up duration, growth hormone, pubertal status, hemoglobin level, and total WBC count at presentation were not predictive of increased LV end-systolic stress. CONCLUSION: There was a reduced incidence and severity of cardiac abnormalities with the lower anthracycline dose protocols (90 to 270 mg/m2) studied compared with previous reports in which subjects had received moderate anthracycline doses (approximately 300 to 550 mg/m2). Cumulative anthracycline dose within the range 90 to 270 mg/m2 did not relate to cardiac abnormalities. This suggests that there may be no safe anthracycline dose to avoid late cardiotoxicity, but reinforces the use of the protocol that affords best survival within the dose range studied.

Adolescent↗

PubMed1996

Prospective study of the incidence and determinants of arrhythmia after total cavopulmonary connection.

BACKGROUND: Atrial distension after Fontan operation may predispose to arrhythmia. Modifications aimed at decreasing the extent of right atrial distension (total cavopulmonary connection, TCPC) have been associated with a lower incidence of early arrhythmia, but serial evaluation has not been performed. METHODS AND RESULTS: All 119 patients undergoing TCPC between March 1987 and December 1993 were enrolled in a prospective study to evaluate the incidence and determinants of arrhythmia by use of ambulatory ECG (AECG) monitoring. Median age at surgery was 5.9 years (range, 0.5 to 19.7 years), and median follow-up was 4.9 years (2.0 to 8.7 years). AECGs were performed before and after surgery and serially during follow-up. There were 17 early deaths, including 8 among 20 patients who had new arrhythmia documented in the operating in the operating room or intensive care unit. For the 102 patients who survived > 30 days after surgery, the proportion free of new AECG arrhythmia or first arrhythmic symptoms was 93% (CI, 89% to 99%) at 2 years and 78% (CI, 66% to 90%) at 5 years. Actuarial analysis treats occurrence of arrhythmia as permanent; however, most of the arrhythmia during follow-up was transient, so that the proportion of patients without arrhythmia was similar before and during follow-up. To date, there has been only 1 late arrhythmic death. CONCLUSIONS: The low prevalence of clinically important arrhythmia during medium-term follow-up supports the TCPC as the preferred option for Fontan surgery.

Adolescent↗

PubMed1996

Laser palliation of inoperable malignant dysphagia: initial and at death.

BACKGROUND: Nd: YAG laser therapy has been shown to be highly effective in the palliation of dysphagia due to inoperable esophageal malignancy. However, the duration of response and the degree of palliation present at death have not been adequately addressed. METHODS: Seventy consecutive patients with inoperable malignant dysphagia (mean age, 70 years; 48 men, 22 women) underwent palliative laser therapy. Dysphagia was assessed on a 5-point scale (0, normal; 4, complete dysphagia) before and after laser therapy and within 2 weeks of death. RESULTS: Ninety-six percent of patients were palliated initially (70% successful, 26% partial). Mean swallowing score improved from 2.3 to 1.1 (p < 0.001) with a mean of 1.9 initial treatment sessions. Swallowing score remained improved in the last two weeks of life at a mean of 1.7 (p < 0.001). Seventy-three percent of patients were palliated at death (36% successful, 37% partial); median survival was six months. The mean total number of laser sessions was 3.4, with a mean time interval between laser sessions of 27.2 days. Complications included one perforation (1.4%) resulting in death. CONCLUSION: Endoscopic laser therapy provides safe and effective initial palliation of inoperable malignant dysphagia. In the majority of patients the palliation is maintained until death.

Aged↗

PubMed1995

Results of heart-lung transplantation in children with cystic fibrosis.

Children with cystic fibrosis represent the largest group referred for, and undergoing, heart-lung transplantation at our institute. Between June 1988 and July 1993, 76 patients were accepted for transplantation, of whom 25 were transplanted, while a further 36 died waiting. Those transplanted ranged from 5-18 years of age and included 13 males and 12 females. Organs were used from donors matched by ABO blood group, size and cytomegalovirus (CMV) status. Post-transplant maintenance immunosuppression comprised cyclosporin A, azathioprine and prednisolone. Anti-thymocyte globulin and high dose methylprednisolone were given peri-operatively and for acute rejection episodes. Actuarial survival was 67% at 1 year, 61% at 2 years and 54% at 3 years. Obliterative bronchiolitis (OB) has occurred in 13 patients (52%) and was the major cause of mortality and morbidity. In three patients, OB was associated with the development of tracheal anastomotic stenosis. Other complications included diabetes mellitus (n = 9), pancreatitis (n = 1) and hypertension (n = 8). Despite these problems, those surviving the first year post-transplant showed a mean FEV1 of 71% (compared to 29% pre-transplant) and enjoyed an overall improved quality of life.

Actuarial Analysis↗

PubMed1995

Oesophageal cancer: outcome of modern surgical management.

Many clinicians still associate oesophagectomy for oesophageal carcinoma with low cure rates, poor palliation and prohibitive peri-operative mortality. Surgical advances have rendered such perceptions inaccurate. A prospective study of all patients undergoing surgery for oesophageal cancer in an Australian teaching hospital between 1979 and 1993 has been undertaken. Selection, staging, pre-operative preparation, surgical technique and postoperative care were all carefully controlled. One hundred and thirty-seven patients were explored. Twenty-one were inoperable. One hundred and sixteen underwent resection with intent to cure. Hospital mortality for oesophagectomy was 1.7%. There were no cases of clinical anastomotic leakage. Eighty-nine per cent achieved excellent to good swallowing. The median survival for all cases was 14 months and the 5 year survival was 18%. Median survival for resected cases was 18 months and the 5 year survival was 26%. The long-term survival was related to postoperative stage of the disease but not to tumour type. Oesophagectomy for oesophageal cancer will restore good swallowing in 90% of cases. Operative mortality should be less than 5% and the overall 5 year survival 20-30%. Early tumours can often be cured (ca in situ 100%, stages I and II 50-60%), indicating the benefits of early detection. Poor survival in advanced disease (stage III 15%, stage IV 0%) on a background of low surgical mortality indicate the need for better staging and more effective adjuvant therapies.

Adenocarcinoma↗

PubMed1995

Supravalvar mitral stenosis: risk factors for recurrence or death after resection.

OBJECTIVE: To assess the medium term outcome in infants and children after surgical resection of supravalvar mitral stenosis with special reference to risk factors for mortality or recurrence of supravalvar mitral stenosis. No detailed follow up has been previously reported in this uncommon condition. DESIGN: Prospective cross sectional clinical and echocardiographic follow up. SETTING: Paediatric cardiothoracic unit. PATIENTS AND METHODS: 23 consecutive children (14 male, nine female, mean age 3 years 2 months at surgery) who underwent resection of supravalvar mitral stenosis between 1978 and 1993. RESULTS: Follow up was for a mean of 58 months (range 0.5-167) after resection of supravalvar mitral stenosis. Four patients developed recurrent supravalvar mitral stenosis: this has not been reported previously. This was recognised 14-108 months after resection and confirmed at repeat operation. Three of these patients had successful reoperations but one died. Five other patients died. On multivariate analysis the only variable associated with survival free of recurrent supravalvar mitral stenosis was older age (18 months or more) at time of surgery (hazard ratio 0.17, 95% confidence interval (CI) 0.03 to 0.95, P < 0.05). Five year actuarial survival free of recurrent obstruction when supravalvar mitral stenosis was resected at age less than 18 months was only 39% (95% CI 9 to 69%) compared with 73% (95% CI 24 to 93%) in older patients. CONCLUSION: Supravalvar mitral stenosis is part of a spectrum of obstructive lesions affecting the left heart. Recurrent supravalvar mitral stenosis can develop after surgical resection. The prognosis in those who require resection within the first 18 months of life is poor: mortality is high, as is the risk of recurrent supravalvar mitral stenosis in survivors, probably because of continuing turbulent flow across a small left ventricular inflow tract.

Age Factors↗

PubMed1995

Cardiac function in Wilms' tumor survivors.

PURPOSE: To study late cardiac function in a single diagnostic group (children with Wilms' tumor) with good long-term survival; to compare patients treated with anthracyclines (doxorubicin) with patients treated without anthracyclines and with a normal child/adolescent group; and to examine the risk factors involved in late cardiac dysfunction. PATIENTS AND METHODS: Echocardiographic studies were performed on 97 Wilms' tumor patients treated with anthracyclines (mean cumulative dose, 303 mg/m2) with a mean follow-up time of 7.1 years, on 39 Wilms' tumor patients treated without anthracyclines with a mean follow-up time of 8.9 years, and on 50 normal subjects. Left ventricular (LV) dimensions, end systolic wall stress (a measure of afterload), and load-dependent and -independent measures of contractility were compared between groups. Potential risk factors, including age at diagnosis, follow-up duration, sex, pubertal status, cardiac irradiation, dose-intensity, and cumulative dose of anthracyclines, were studied by multivariate analysis. RESULTS: Twenty-five percent of the anthracycline-treated group showed cardiac abnormalities. All but one of these patients had increased LV afterload. Risk factors for increased afterload were anthracycline cumulative dose (P < .05) and anthracycline dose-intensity (P < .02). Wilms' tumor patients treated without anthracyclines had thickened LV walls compared with normal subjects (P < .05). CONCLUSION: Total dose and dose-intensity of anthracycline were risk factors for increased LV afterload in long-term Wilms' tumor survivors treated on standard protocols. The increase in afterload accounted for reduced LV shortening, whereas contractility was rarely abnormal. The new finding that Wilms' tumor survivors who do not receive anthracyclines have mild LV hypertrophy may provide some protection against anthracycline-induced cardiotoxic effects.

Adolescent↗

PubMed1995

Late outcome of survivors of intervention for neonatal aortic valve stenosis.

BACKGROUND: This study examined the late outcome after intervention for neonatal aortic valve stenosis. METHODS: Seventy-three neonates (59 boys and 14 girls) underwent intervention for critical aortic valve stenosis during the first 30 days of life at two institutions, The Hospital for Sick Children, London, and Duke University Medical Center, Durham, North Carolina. Procedures performed include closed valvotomy (n = 12), open valvotomy with inflow occlusion (n = 14), open valvotomy with cardiopulmonary bypass (n = 33), balloon valvotomy (n = 12), and other procedures (n = 2). The mean age at the first intervention was 8 +/- 1 days. RESULTS: The hospital mortality was 52.1%. The mean duration of follow-up for the hospital survivors (n = 35) was 8.3 +/- 1.1 years. The actuarial survival for the hospital survivors was 93.3% +/- 4.7% at 10 years and 83.9% +/- 9.8% at 15 years, whereas event-free survival (reintervention, endocarditis, or early death) was 61.8% +/- 9.3% at 5 years, 34.2% +/- 10.8% at 10 years, and 27.4% +/- 10.6% at 15 years. Three patients have died and 11 patients have required aortic valve replacement during the follow-up period. The age at the initial intervention, the type of initial intervention, and the year of initial intervention were not predictive of early death or need for reintervention. At last follow-up, 26 of the long-term survivors (n = 32) were in functional class I and 6 were in functional class II. CONCLUSIONS: Aortic stenosis in the neonatal period is a difficult problem with a high initial mortality. Late survival and functional class are excellent for patients surviving the initial hospitalization, but most require further intervention within 10 years.

Aortic Valve Stenosis↗

PubMed1994

Endothelium-dependent dilation in the systemic arteries of asymptomatic subjects relates to coronary risk factors and their interaction.

OBJECTIVES: This study attempted to assess whether coronary risk factors are associated with endothelial dysfunction in the systemic arteries of asymptomatic men and women. BACKGROUND: Endothelial dysfunction is present in adults with established atherosclerosis. It is not known whether risk factors interact to produce endothelial dysfunction in clinically well subjects early in the natural history. METHODS: Using high resolution ultrasound, we measured arterial diameter at rest, after reactive hyperemia (with increased flow causing endothelium-dependent dilation) and after sublingual nitroglycerin (an endothelium-independent dilator). Arterial responses were studied noninvasively in 500 clinically well, nonhypertensive subjects (252 men, 248 women; mean [+/- SD] age 36 +/- 15 years, range 5 to 73), including 179 current and former smokers. The superficial femoral artery was studied in 46 subjects and the brachial artery in 454. RESULTS: Flow-mediated dilation ranged from -1% to +17%. All arteries dilated in response to administration of nitroglycerin (17 +/- 6%), suggesting an abnormality of endothelial function in subjects with impaired flow-mediated dilation. On univariate analysis, reduced flow-mediated dilation was significantly related to hypercholesterolemia, cigarette smoking, higher blood pressure, male gender, older age, family history of premature vascular disease and larger vessel size (p < 0.01). By multiple stepwise regression analysis, reduced flow-mediated dilation was independently associated with cigarette smoking, older age, male gender and larger vessel size (p < 0.005) but not with total cholesterol level, blood pressure or family history. A composite risk factor score was independently related to flow-mediated dilation (r = -0.30, p < 0.0001), suggesting risk factor interaction. CONCLUSIONS: Loss of endothelium-dependent dilation in the systemic arteries occurs in the preclinical phase of vascular disease and is associated with interaction of the same risk factors known to predispose to atherosclerosis and its complications in later life.

Adolescent↗

PubMed1994

Thrombosis and embolism in long-term central venous access for parenteral nutrition.

Although the use of silicone catheters for long-term central venous access is widespread, little is known about the incidence of pulmonary thromboembolic complications. We studied clinical events, lung perfusion scans, and echocardiographic screens in 34 children and adolescents with gut failure who had received cyclical parenteral nutrition for 2 months to 9 years. Major thrombosis and/or embolism was identified in 12 patients and 4 died as a consequence. Actuarial survival free from thrombosis was 53% at 5 years (95% Cl, 30-77%). Survival free from fatal pulmonary thromboembolic events was 74% at 5 years (48-99%). 3 patients required surgery to remove right atrial thrombus or pulmonary emboli. Major right atrial thrombosis and pulmonary embolism are common and potentially fatal complications of parenteral nutrition by long-term venous access in childhood. Anticoagulation is recommended.

Adolescent↗

PubMed1994

Ebstein's anomaly: presentation and outcome from fetus to adult.

OBJECTIVES: This study was conducted to investigate the presentation and outcome of patients with Ebstein's anomaly of the tricuspid valve. BACKGROUND: Ebstin's anomaly may present at any age and has a highly variable clinical course. Previous natural history studies have been based on clinical and angiographic diagnosis and have included mainly older children and adults. Echocardiography, however, has facilitated fetal and neonatal diagnosis so that the natural history needs to be redefined. METHODS: We reviewed 220 cases of Ebstein's anomaly presenting from fetal to adult life between 1958 and 1991, with 1 to 34 years of follow-up. RESULTS: The most common presentation in each age group was abnormal routine prenatal scan for fetuses (86%), cyanosis for neonates (74%), heart failure for infants (43%), incidental murmur for children (63%) and arrhythmia for adolescents and adults (42%). Early presentation was frequently associated with other cardiac lesions, usually pulmonary stenosis or atresia. Surgery was undertaken at some stage in 86 (39%) of the 220 patients. Actuarial survival for all liveborn patients was 67% at 1 year and 59% at 10 years. There were 58 deaths, including 26 from heart failure, 19 perioperative and 8 sudden. Predictors of death included echocardiographic grade of severity at presentation (relative risk 2.7 for each increase in grade, 95% confidence limits 1.6 to 4.6), fetal presentation (6.9, confidence limits 1.6 to 16.5) and right ventricular outflow tract obstruction (2.1, confidence limits 1.1 to 4.4). Morbidity was mainly related to arrhythmias and late hemodynamic deterioration. Of 155 survivors, 129 (83%) were in functional class 1 and 104 (67%) were receiving no medical therapy. CONCLUSIONS: In Ebstein's anomaly, fetal and neonatal presentation is associated with a poor outcome and can be predicted by the echocardiographic appearance and presence of associated lesions. In older children and adults, incidental findings and arrhythmia are common and the long-term outcome is superior.

Adolescent↗

PubMed1994

Dilated cardiomyopathy in children: determinants of outcome.

OBJECTIVE: To determine the outcome of dilated cardiomyopathy presenting in childhood and the features that might be useful for prognostic stratification. SETTING: Supraregional paediatric cardiology unit. DESIGN: Retrospective analysis. BACKGROUND: The natural history of dilated cardiomyopathy in children is not well characterised. Previous studies have shown a variable relation between age at presentation and outcome, and sudden death has been infrequent. METHODS: Retrospective study of 63 consecutive patients with idiopathic dilated cardiomyopathy presenting between 1979 and 1992. Survival curves were constructed by the Kaplan-Meier method. RESULTS: Age at diagnosis ranged from 1 day to 15 years (median 12 months) and follow up ranged from 1 day to 13 years (median 19 months). Actuarial survival from presentation was 79% at one year (95% confidence interval (95% CI) 66%-88%) and 61% (44%-74%) at five years. Univariate analysis showed that mural thrombus, left ventricular end diastolic pressure > 20 mm Hg, and age at presentation > 2 years were predictors of adverse outcome, but on multivariate analysis only age at presentation was significant. Left ventricular echocardiographic indices either did not improve or deteriorated in 36 children (17 of whom died, four suddenly, and three were transplanted), partially improved in 16 (three of whom died, all suddenly), and returned to normal in 11 (all of whom have survived). CONCLUSIONS: Older age at presentation and lack of improvement in systolic function are associated with an adverse outcome, and early transplantation should be considered in these patients. There is a persistent risk of late sudden death in those children in whom echocardiographic dimensions remain abnormal.

Adolescent↗

PubMed1994

Analysis of a cluster of surgical failures. Application to a series of neonatal arterial switch operations.

A pediatric cardiac surgeon performed 104 neonatal arterial switch operations for transposition of the great arteries with or without ventricular septal defect between June 1987 and February 1993. Initial euphoria on having only one death in the first 52 patients gave way to increasing concern when patients 53, 55, 59, 63, 64, 67, and 68 died. Sensing a problem, the surgeon visited a low-risk institution after patients 55 and 64 had died and then decided to re-train after patient 68 died. One death has occurred since. To find out whether the cluster of failures could have been related to chance alone, to variability of risk factors across time, or to suboptimal performance, we conducted the following analyses: First, identification of trends with the cumulative sum procedure was undertaken and actual mortality compared with the mortality predicted from an equation derived from a multi-institutional study. Second, logistic regression analysis of risk factors was done. If a mechanism of continuous monitoring had been in place, unfavorable trends and a need for change in protocol would have been detected earlier. Retrospective risk factor analysis suggested an excessive risk for patients with origin of the circumflex or left anterior descending coronary arteries from sinus 2 and a protective effect of phenoxybenzamine. However, about half of the risk associated with the cluster of failures was not accounted for by the variables analyzed. There was therefore an indication of suboptimal performance that appears to have been neutralized by retraining.

Cardiac Surgical Procedures↗

PubMed1994

Outcome measures for the neonatal management of pulmonary atresia with intact ventricular septum.

The outcome in 135 patients with pulmonary atresia with intact ventricular septum was reviewed in terms of actuarial survival and "suitability" for eventual definitive repair (defined as having a tricuspid valve diameter larger than 2.4 standard deviations below the mean normal beyond the neonatal period). Of patients who underwent an initial closed valvotomy, 50% were dead, 22% were alive and suitable, and the remaining 28% were alive but unsuitable for definitive repair at 5 years. None of 66 patients who underwent primary shunt alone achieved suitability and 52% were dead at 5 years. No mode of neonatal closed valvotomy was consistently satisfactory: in only 10 of 26 survivors with serial measurements did the neonatal valvotomy alone achieve decompression to subsystemic pressures. Only half of the decompressed ventricles achieved growth of the tricuspid valve disproportionate to somatic growth as a result of the neonatal procedure. Strategies for the neonatal treatment of pulmonary atresia with intact ventricular septum should not rely on closed operations on the pulmonary valve to optimized right ventricular growth.

Actuarial Analysis↗

PubMed1993

Outer membrane protein YadA of enteropathogenic yersiniae mediates specific binding to cellular but not plasma fibronectin.

The binding of bacteria or bacterial products to host proteins of tissue extracellular matrix may be a mechanism of tissue adherence. We investigated interactions of the plasmid-encoded outer membrane protein YadA, which confers pathogenic functions on enteropathogenic yersiniae, with fibronectin. Attachment of YadA-positive and YadA-negative recombinant Yersinia enterocolitica strains to cartilage-derived human cellular fibronectin and human plasma fibronectin in the solid phase revealed that YadA mediates binding of yersiniae to cellular fibronectin in a saturable, concentration-dependent manner. The interaction could be inhibited by an anti-YadA-specific anti-serum. An anti-beta 1-integrin antibody and the synthetic peptide G-R-G-D-S-P, representing the binding site for alpha 5 beta 1-integrin on fibronectin, did not block attachment of YadA-positive yersiniae to cellular fibronectin, indicating a binding site for YadA on cellular fibronectin independent of the R-G-D-S-containing site. By contrast, YadA failed to mediate binding to plasma fibronectin immobilized on nitrocellulose or plastic surfaces. These observations provide evidence for the hypothesis that the binding region for YadA in cellular fibronectin is not present in plasma fibronectin. This study is the first report on differential binding of bacteria to splicing variants of fibronectin. Further experiments might answer the question whether binding of YadA to cellular fibronectin contributes to the pathogenesis of yersiniae, both to the initial adhesion of the bacteria to the matrices of the host and to the arthritogenic potential of enteropathogenic yersiniae.

Adhesins, Bacterial↗