Search PubMed⌕ Search

Biomedical subjects

John Hess

Publications and source records attributed to John Hess.

At least 37 records · Page 2Linked to original sources
PubMed2005

The expression of the NADPH oxidase subunit p22phox is regulated by a redox-sensitive pathway in endothelial cells.

Endothelial dysfunction is characterized by increased levels of reactive oxygen species (ROS) and a prothrombotic state. The mechanisms linking thrombosis to ROS production in the endothelium are not well understood. We investigated the role of thrombin in regulating NADPH oxidase-dependent ROS production and expression of its subunit p22phox in the endothelial cell line EaHy926. Thrombin elicited a biphasic increase in ROS generation peaking within 15 min, but also at 3 h. The delayed response was accompanied by increased p22phox mRNA and protein expression. Two-photon confocal laser microscopy showed colocalization between p22phox and ROS production. Antioxidant treatment with vitamin C or diphenyleneiodonium abrogated thrombin-induced ROS production and p22phox expression, whereas H2O2 elevated ROS production and p22phox levels. Both responses were dependent on p38 MAP kinase and phosphatidylinositol-3-kinase (PI3 kinase)/Akt. Finally, p22phox was required for thrombin- or H2O2-stimulated proliferation. These data show that thrombin rapidly increases ROS production in endothelial cells, resulting, via activation of p38 MAP kinase and PI3 kinase/Akt, in upregulation of p22phox accompanied by a delayed increase in ROS generation and enhanced proliferation. These findings suggest a positive feedback mechanism whereby ROS, possibly generated by the NADPH oxidase, lead to elevated levels of p22phox and, thus, sustained ROS generation as is observed in endothelial dysfunction.

Blotting, Western↗
PubMed2005

Diagnostic power of aortic elastic properties in young patients with Marfan syndrome.

BACKGROUND: In patients with Marfan syndrome, progressive aortic dilation implicates a still-unpredictable risk of life-threatening aortic dissection and rupture. We sought to quantify aortic wall dysfunction noninvasively, determine the diagnostic power of various aortic parameters, and establish a diagnostic model for the early detection of aortic abnormalities associated with Marfan syndrome. METHODS: In 19 patients with Marfan syndrome (age, 17.7 +/- 9.5 years) and 19 age- and sex-matched healthy control subjects, computerized ascending and abdominal aortic wall contour analysis with continuous determination of aortic diameters was performed out of transthoracic M-mode echocardiographic tracings. After simultaneous oscillometric blood pressure measurement, aortic elastic properties were determined automatically. RESULTS: The following ascending aortic elastic parameters showed statistically significant differences between the Marfan group and the control group: (1) decreased aortic distensibility ( P < .001), (2) increased wall stiffness index ( P < .01), (3) decreased systolic diameter increase ( P < .01), and (4) decreased maximum systolic area increase ( P < .001). The diagnostic power of all investigated parameters was tested by single logistic regression models. A multiple logistic regression model including solely aortic parameters yielded a sensitivity of 95% and a specificity of 100%. CONCLUSIONS: In young patients with Marfan syndrome, a computerized image-analyzing technique revealed decreased aortic elastic properties expressed by parameters showing high diagnostic power. A multiple logistic regression model including merely aortic parameters can serve as useful predictor for Marfan syndrome.

Adolescent↗
PubMed2005

Need for closure of secundum atrial septal defect in infancy.

OBJECTIVES: Closure of isolated secundum atrial septal defect is generally recommended at the age of 4 to 5 years. However, there are children with isolated secundum atrial septal defect in whom early closure should be performed. We aimed to assess the underlying conditions that led to earlier closure in this special patient group and to analyze the outcome. METHODS AND RESULTS: From January 1990 through August 2002, 24 infants with isolated secundum atrial septal defect underwent surgical closure within the first year of life. All children were symptomatic. Signs of pulmonary hyperperfusion, such as tachydyspnea, failure to thrive, recurrent respiratory infections, or heart failure, were present. Four infants required artificial ventilation. Ten patients had additional problems, such as prematurity with chronic lung disease, hepato-omphalocele and congenital diaphragmatic hernia, which were present in 1 patient each. Eleven patients had defined dysmorphic syndromes. All but 1 infant underwent preoperative invasive hemodynamic evaluation. Thirteen patients had pulmonary hypertension preoperatively. The follow-up time was 46 +/- 33 months (range, 4-125 months). At follow-up, pulmonary artery pressure proved to be normal in 11 of the 13 children who had pulmonary hypertension previously. One patient died of persistent pulmonary hypertension. Clinical performance, growth, and development improved in nearly all patients. All ventilator-dependent children could be weaned shortly after atrial septal defect closure. CONCLUSIONS: If lungs are compromised, even a minor left-to-right shunt might be poorly tolerated in infancy. In these children early surgical closure of an isolated secundum atrial septal defect should be performed to support thrive and growth and to prevent the onset of irreversible changes of the pulmonary vasculature.

Cardiac Surgical Procedures↗
PubMed2005

Congenital and surgically acquired Wolff-Parkinson-White syndrome in patients with tricuspid atresia.

OBJECTIVES: There are reports associating an increased incidence of Wolff-Parkinson-White syndrome with tricuspid atresia. Here we report on electrophysiologic studies in patients with tricuspid atresia and Wolff-Parkinson-White syndrome after the Fontan operation. In these patients the atrial arrhythmia often seen in patients undergoing the Fontan operation triggered atrioventricular re-entrant tachycardia or caused life-threatening arrhythmias. METHODS: Five patients with tricuspid atresia after palliation with a modified Fontan operation (atrioinfundibular connections) and Wolff-Parkinson-White syndrome are presented. RESULTS: Four of these patients had symptomatic paroxysmal orthodromic atrioventricular re-entrant tachycardia and a history of syncope; one of them additionally had atrial flutter with 2:1 conduction to the ventricle. A fifth patient presented with a life-threatening broad-complex tachycardia. In electrophysiologic studies an accessory pathway was localized in the right septal area in 3 patients. In 2 patients the accessory atrioventricular pathways were created by means of surgical intervention, connecting the right atrial appendage to the right ventricular outflow tract. All patients could be managed successfully by means of catheter ablation. CONCLUSIONS: In patients with tricuspid atresia, there are congenital and surgically acquired accessory pathways responsible for the increased rate of Wolff-Parkinson-White syndrome. Both types of accessory pathways can and should be treated by means of catheter ablation because atrial arrhythmia often seen in patients undergoing the Fontan operation can trigger atrioventricular re-entrant tachycardia or cause life-threatening tachycardia. Congenital accessory pathways should be excluded carefully before surgical intervention for total cavopulmonary anastomosis in patients with tricuspid atresia.

Adolescent↗
PubMed2005

Assumed oxygen consumption frequently results in large errors in the determination of cardiac output.

OBJECTIVE: We sought to investigate the differences in assumed and measured oxygen consumption values for the determination of cardiac output by using the Fick principle in a pediatric population with congenital heart disease. METHODS: The patient population consisted of 143 patients with a mean age of 11.3 years (age range, 2 days to 23.8 years) undergoing cardiac catheterization during general anesthesia and with mechanical ventilation. Oxygen consumption was measured with a standard commercial analyzing system (Deltatrac II; Datex, Engström, Helsinki, Finland). Assumed oxygen consumption values were calculated according to the formulas of Krovetz and Goldbloom and LaFarge and Miettinen. Comparisons between measurements and assumptions were performed by Bland-Altman plots. Two-sided paired t tests were used to assess a difference of the assumed and measured values. RESULTS: The range of measured oxygen consumption values was between 55.2 and 249 mL . min -1 . m -2 . The Krovetz-Goldbloom formula led to systematically larger values compared with the measured values (P = .0001; mean difference of -53.3 mL . min -1 . m -2 ; 95% confidence interval, -56.7 to -49.8 mL . min -1 . m -2 ). The use of the LaFarge-Miettinen formula tends to overestimate oxygen consumption (P = .0037; mean difference of -15.9 mL . min -1 . m -2 ; 95% confidence interval, -26.5 to -5.4 mL . min -1 . m -2 ). A similarly poor agreement was found when analyzing a subgroup of 25 patients with Fontan-type circulation. CONCLUSION: The use of assumed instead of measured oxygen consumption values introduces large errors in the determination of cardiac output.

Adolescent↗
PubMed2005

Safety of uncrossmatched type-O red cells for resuscitation from hemorrhagic shock.

BACKGROUND: Uncrossmatched type-O packed red blood cells (UORBC) are recommended for immediate transfusion in hemorrhaging trauma patients. The potential for alloimmunization with this technique is controversial, and has been reported to be as high as 80%. We examined a 1-year experience with UORBC transfusion to determine the incidence of allergic reaction and alloimmunization. METHODS: Blood Bank and Trauma Registry databases for the year 2000 were linked to determine the incidence of UORBC use and the characteristics of patients, including the incidence of transfusion reactions and seroconversion of Rh-patients. Ten units of type-O, Rh+ blood (and two units of O-blood for women of childbearing age) were available for immediate transfusion, 30 to 45 minutes sooner than type-specific or crossmatched red blood cells. UORBC were administered to any patient with signs of severe hemorrhagic shock, at the discretion of the attending physician. RESULTS: In all, 480 trauma patients (out of 5,623 admitted) received transfusions of RBC, totaling 5,203 units. Five hundred eighty-one units of UORBC were given to 161 patients. Average Injury Severity Score in the UORBC cohort was 33.8. Patients receiving UORBC received an average of 16.9 total units of red blood cells, 14 units of plasma, and 10 units of platelets. Seventy-three patients died (45%). There were no acute hemolytic transfusion reactions observed in the patients who received UORBC. Four Rh-women received UORBC, all O-. Ten Rh-men received O+ blood, and only one developed antibodies to the Rh antigen. CONCLUSION: The need for UORBC is associated with significant injury and the need for subsequent massive transfusion. In this largest reported trauma series, the use of UORBC enabled rapid administration of red cells to hemorrhaging patients, without discernible risk for transfusion-related complications. The rate of seroconversion of Rh-patients is lower than reported in the literature, perhaps due to immune suppression associated with hemorrhagic shock.

ABO Blood-Group System↗
PubMed2005

Thrombin activates the p21-activated kinase in pulmonary artery smooth muscle cells. Role in tissue factor expression.

The p21-activated serine/threonine kinases (PAK) play an important role in a variety of cellular functions. However, their role in the smooth muscle response to thrombin, which is activated upon vascular injury and promotes vascular remodelling processes, is not resolved. Here we investigated the role of PAK in thrombin signalling and regulation of tissue factor (TF), the activator of the extrinsic coagulation cascade, in pulmonary artery smooth muscle cells (PASMC), the main cell type responsible for vascular remodelling in pulmonary hypertension. PAK was rapidly phosphorylated in response to thrombin. Thrombin and active PAKT423E phosphorylated p38 MAP kinase (p38MAPK), ERK1/2, phosphatidylinositol-dependent kinase-1 (PDK1) and protein kinase B/Akt (PKB) whereas kinase-deficient PAK1 prevented activation of these kinases by thrombin. In addition, kinase- deficient MKK3 inhibited activation of PDK1 and PKB by thrombin. Further, thrombin and active PAK1 induced TF expression and promoter activity while kinase-deficient PAK1 diminished thrombin-induced TF upregulation. Moreover, kinase-deficient MKK3, PDK1 and PKB inhibited thrombin- and PAK-dependent TF expression and promoter activity. Together these findings show that PAK is a critical element of thrombin signalling in PASMC which is involved in the regulation of TF expression by sequentially activating MKK3/p38MAPK, PDK1 and PKB. Thus, PAK may play an important role in promoting vascular remodelling processes in pulmonary hypertension.

3-Phosphoinositide-Dependent Protein Kinases↗
PubMed2005

Marfan syndrome: what internists and pediatric or adult cardiologists need to know.

Marfan syndrome (MFS) is one of the most frequent connective tissue disorders, showing striking pleiotropism and clinical variability. There is autosomal dominant inheritance with complete penetrance but variable expression. Approximately 25% of MFS patients have no family history of the syndrome and represent sporadic cases due to new mutations. This hazardous condition is often associated with premature cardiovascular death unless surveillance and management are optimized. The fibrillin gene (FBN1) encodes the structure of the connective tissue protein fibrillin. MFS is caused by mutations in the fibrillin gene, located on chromosome 15 at locus 15q21. Fibrillin abnormalities reduce the structural integrity of different body systems, primarily involving the heart valves, blood vessels, lungs, bones, tendons, ligaments, cartilages, eyes, skin, spinal dura and the CNS. Patients with MFS are likely to have too little fibrillin within these structures, resulting in clinically relevant problems. For example, in the aortic wall, deficient fibrillin may trigger progressive aortic ectasia and may result in aortic dissection.

Adult↗
PubMed2004

Human urotensin II is a novel activator of NADPH oxidase in human pulmonary artery smooth muscle cells.

BACKGROUND: Human urotensin II (hU-II) is a potent vasoactive peptide possibly involved in pulmonary hypertension. Because the signaling mechanisms activated by this peptide in the pulmonary vasculature are largely unknown, we investigated the role of hU-II in the activation of NADPH oxidase and the control of redox-sensitive kinase pathways, expression of plasminogen activator inhibitor-1 (PAI-1), and proliferation in pulmonary artery smooth muscle cells (PASMCs). METHODS AND RESULTS: hU-II upregulated expression of the NADPH oxidase subunits p22phox and NOX4 and increased the levels of reactive oxygen species (ROS), which were abrogated by transfecting p22phox or NOX4 antisense vectors. p22phox and NOX4 also contributed to hU-II-induced activation of extracellular signal-regulated kinase 1/2, p38 mitogen-activated protein kinase, c-Jun N-terminal kinase, and protein kinase B (Akt). Furthermore, hU-II increased the expression of PAI-1 and enhanced PASMC proliferation in an NADPH oxidase- and kinase-dependent manner. CONCLUSIONS: hU-II is a potent activator of ROS generation by NADPH oxidase in PASMCs, leading to redox-sensitive activation of mitogen-activated protein kinases and Akt and subsequently to enhanced PAI-1 expression and increased proliferation. These findings suggest that hU-II may play a novel role in pulmonary hypertension by promoting remodeling processes via activation of NADPH oxidases.

Antisense Elements (Genetics)↗
PubMed2004

Surgical treatment of patent ductus arteriosus: a new historical perspective.

The conventional surgical history of ligation of a patent ductus arteriosus (PDA) dates from August 26, 1938, when Robert E. Gross of Boston, Massachusetts, successfully ligated a PDA. It is largely unknown that in the same year and before Gross, Emil Karl Frey, a Surgeon at the Medizinische Akademie in Dusseldorf, Germany, already ligated a PDA successfully. Assuming that he would soon perform more ligations, Frey did not publish his findings, and this historic ductal operation escaped attention.

Cardiac Surgical Procedures↗
PubMed2004

Erythrocyte indexes, iron metabolism, and hyperhomocysteinemia in adults with cyanotic congenital cardiac disease.

A high percentage of cyanotic adults (37%) with cyanotic congenital cardiac disease (CCD) presented with depleted iron stores (13 of 52) or latent iron deficiency (6 of 52), even in a CCD center in which cyanotic patient phlebotomy is mostly avoided. In many of these patients, hypochromia and microcytosis was frequent, whereas hyperchromia and macrocytosis were relatively common.Furthermore, 50% of patients presented with hyperhomocysteinemia, possibly related to folate or B vitamin deficiencies, which may increase red blood cell size and color, explaining the lack of microcytosis and hypochromia in many cyanotic patients with iron deficiency.

Adolescent↗
PubMed2004

Chronic endothelin A receptor blockade in lambs with increased pulmonary blood flow and pressure.

Endothelin receptor blockade is an emerging therapy for pulmonary hypertension. However, hemodynamic and structural effects and potential changes in endogenous nitric oxide (NO)-cGMP and endothelin-1 signaling of chronic endothelin A receptor blockade in pulmonary hypertension secondary to congenital heart disease are unknown. Therefore, the objectives of this study were to determine hemodynamic and structural effects and potential changes in endogenous NO-cGMP and endothelin-1 signaling of chronic endothelin A receptor blockade in a lamb model of increased pulmonary blood flow following in utero placement of an aortopulmonary shunt. Immediately after spontaneous birth, shunt lambs were treated lifelong with either an endothelin A receptor antagonist (PD-156707) or placebo. At 4 wk of age, PD-156707-treated shunt lambs (n = 6) had lower pulmonary vascular resistance and right atrial pressure than placebo-treated shunt lambs (n = 8, P < 0.05). Smooth muscle thickness or arterial number per unit area was not different between the two groups. However, the number of alveolar profiles per unit area was increased in the PD-156707-treated shunt lambs (190.7 +/- 5.6 vs. 132.9 +/- 10.0, P < 0.05). Plasma endothelin-1 and cGMP levels and lung NOS activity, cGMP, eNOS, preproendothelin-1, endothelin-converting enzyme-1, endothelin A, and endothelin B receptor protein levels were similar in both groups. We conclude that chronic endothelin A receptor blockade attenuates the progression of pulmonary hypertension and augments alveolar growth in lambs with increased pulmonary blood flow.

Animals↗
PubMed2004

Successful primary correction of tetralogy of fallot with pulmonary atresia and aortopulmonary window in a 2,220-g neonate with a valved bovine jugular vein conduit.

Prenatal diagnosis of tetralogy of Fallot with pulmonary atresia (TOF/PA) was confirmed in a newborn with a birth weight of 2,095 g. Additionally, an aortopulmonary window (APW) type I was diagnosed on echocardiography. The operation was performed at the age of 4 weeks due to congestive heart failure. The APW was closed with a pericardial patch, the ventricular septal defect (VSD) with a Dacron patch, and the right ventricular outflow tract (RVOT) was reconstructed with a 12-mm bovine jugular vein valved conduit (Contegra, Medtronic Inc., Minneapolis, MN, USA). At 15-month follow-up, the patient is in excellent clinical condition without medication. On echocardiography, the conduit showed a mean gradient of 11 mmHg with first-degree insufficiency.

Abnormalities, Multiple↗
PubMed2004

Occurrence and management of atrial arrhythmia after long-term Fontan circulation.

OBJECTIVES: In patients after the Fontan operation, we determined risk factors for late failure and for intra-atrial re-entrant tachycardia at 15 to 20 years' follow-up. Midterm results after electrophysiologic ablation therapy for these tachycardias were also evaluated. METHODS: Current follow-up was available in 162 patients (2005 patient-years) with a wide range of underlying diagnoses operated on between February 1978 and May 1995. Risk factor analysis included patient-related and procedure-related variables, with late failure and the incidence of re-entrant tachycardia as outcome parameters. RESULTS: Forty late failures were observed (2.0 per 100 patient-years). At 15 years, Kaplan-Meier estimated survival was significantly (P =.007) better for patients with tricuspid atresia (93%) compared with that for patients with complex congenital malformation (71%). The sole multivariable risk factor for Fontan failure was the type of underlying diagnosis. At 20 years' follow-up, overall freedom from tachycardia was estimated to be 46% +/- 12%. Acute success of electrophysiologic ablation was seen in 25 (83%) of 30 patients, and Kaplan-Meier estimated freedom from recurrent tachycardia was 81% +/- 10% at 3 years. Multivariate analysis identified duration of Fontan circulation as the sole risk factor for re-entrant tachycardias. CONCLUSION: After the modified Fontan operation, long-term survival in patients with tricuspid atresia was significantly better compared with that in patients with complex congenital malformations. As first-choice therapy for atrial re-entrant tachycardias, we recommend electrophysiologic ablation therapy.

Adolescent↗
PubMed2004

What was the impact of the introduction of extracardiac completion for a single center performing total cavopulmonary connections?

BACKGROUND: Creation of an extracardiac cavopulmonary connection has been proposed as a superior alternative to the lateral intracardiac tunnel for the completion of total cavopulmonary connection. METHODS AND RESULTS: We made a retrospective review of our experience with 125 patients undergoing a total cavopulmonary connection between June 1994 and January 2003. Our experience with the extracardiac connection for completion began in 1999. Since 1994, we have constructed an intracardiac tunnel in 50 patients, and an extracardiac connection in 75. Of the total number, 83 had undergone an earlier partial cavopulmonary connection. Additional intracardiac procedures were performed in 43 patients at time of completion, in 25 of those undergoing extracardiac completion, and in 18 of the patients having an intracardiac procedure. The mean size of the tube used for completion was 19 mm. The mean cross-clamp time for placement of the intracardiac tunnel was 77 min, with a median of 80.5 min, and a mean cardiopulmonary bypass time of 139 min, with a median of 131 min. For construction of the extracardiac connection, a mean cross-clamp time in 24 of the 75 patients was 54 min, with a median of 54 min. Mean cardiopulmonary bypass time for all the patients with an extracardiac connection was 100 min, with a median of 88 min. Reoperations were needed in 10 patients, 6 having intracardiac and 4 extracardiac procedures. Of these, 5 were early and 5 late, including one take down. None of the patients died after these interventions. Taken overall, 8 patients died, with 5 early deaths. In the multivariable analysis, cardiopulmonary bypass time of more than 120 min, atrioventricular valvar replacement, and banding of the pulmonary trunk prior to the total cavopulmonary connection, all reached statistical significance for early death, whereas only heterotaxy syndrome remained as the sole risk factor for late death. There was no significant difference in survival between the modifications used. DISCUSSION: Whereas we could not identify any clinical superiority for the extracardiac approach in the short-term, the concept of extracardiac completion has helped to simplify the overall procedure. Longer follow-up will be required to elucidate any potential advantages.

Blood Flow Velocity↗