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D R Fischer

Publications and source records attributed to D R Fischer.

At least 19 recordsLinked to original sources
PubMed2006

Application and assessment of a robust elastic motion correction algorithm to dynamic MRI.

The purpose of this study was to assess the performance of a new motion correction algorithm. Twenty-five dynamic MR mammography (MRM) data sets and 25 contrast-enhanced three-dimensional peripheral MR angiographic (MRA) data sets which were affected by patient motion of varying severeness were selected retrospectively from routine examinations. Anonymized data were registered by a new experimental elastic motion correction algorithm. The algorithm works by computing a similarity measure for the two volumes that takes into account expected signal changes due to the presence of a contrast agent while penalizing other signal changes caused by patient motion. A conjugate gradient method is used to find the best possible set of motion parameters that maximizes the similarity measures across the entire volume. Images before and after correction were visually evaluated and scored by experienced radiologists with respect to reduction of motion, improvement of image quality, disappearance of existing lesions or creation of artifactual lesions. It was found that the correction improves image quality (76% for MRM and 96% for MRA) and diagnosability (60% for MRM and 96% for MRA).

Adult↗
PubMed2003

Is the "blooming sign" a promising additional tool to determine malignancy in MR mammography?

The aim of this study was to evaluate potential diagnostic relevance of blooming effect for verification of suspicious breast lesions in MR mammography (MRM). The MRM examinations of 1035 patients, all following the same imaging protocol (from 1994 to 2001) were retrospectively evaluated by two experienced radiologists in consensus. A total of 817 lesions showed a focal enhancement; of these, 793 were histologically verified after surgical intervention so that 514 malignant and 279 benign lesions could be evaluated. Using a 1.5-T Gyroscan ACS II-imager (Philips, Hamburg, Germany) and a double breast coil with the patient lying in a prone position, 0.1 mmol/kgbw Magnevist (Schering, Berlin, Germany) were injected into the cubital vein to obtain dynamic axial and coronal T1-weighted fast-field-echo images every minute up to 7 min after bolus injection. Blooming sign describes a progradient unsharpness of lesion borders initially sharply shaped and fast enhancing 7 min after bolus injection; 324 of 514 (63.0%) malignant lesions and 41 of 279 (14.7%) benign lesions revealed a blooming sign (sensitivity 63.0%, specificity 85.3%, accuracy 70.9%, positive predictive value 88.8%, negative predictive value 56.0%). Forty-one of 279 benign lesions showed a blooming sign; of these, there were 4 of 86 (4.7%) fibroadenomas, 2 of 21 (9.5%) phylloides tumours, 11 of 38 (28.9%) papillomas, 3 of 9 (33.3%) radial scars, 2 of 19 (10.5%) mastitis, 1 of 4 (25%) galactophoritis, 1 of 3 (33.3%) ADH and 19 of 99 (17.2%) mastopathic proliferations, respectively. Blooming sign is a phenomenon which should be taken into account when diagnosing MR mammographies because it might increase the ability to discriminate uncertain breast lesions; however, this effect can only be used as an additional item to other well-known effects such as plateau, washout and cancer corner.

Adult↗
PubMed2001

Dantrolene reduces serum TNFalpha and corticosterone levels and muscle calcium, calpain gene expression, and protein breakdown in septic rats.

The effects of dantrolene on serum TNFalpha and corticosterone levels and on muscle calcium, calpain gene expression, and protein breakdown were studied in rats with abdominal sepsis induced by cecal ligation and puncture. Treatment of rats with 10 mg/kg of dantrolene 2 h before and 8 h after induction of sepsis reduced serum TNFalpha and corticosterone, muscle calcium levels, mRNA levels for m- and mu-calpain, and the muscle specific calpain p94, as well as total and myofibrillar protein breakdown rates, determined as release of tyrosine and 3-methylhistidine, respectively, from incubated extensor digitorum longus muscles. The results support the concept that increased calcium concentrations may be an important mechanism of sepsis-induced muscle protein breakdown. The data also indicate that other mechanisms, in addition to reduced muscle calcium concentrations such as decreased levels of TNFalpha and glucocorticoids, may contribute to the anti-catabolic effects of dantrolene during sepsis. The observations are important from a clinical standpoint because they suggest that the catabolic response in skeletal muscle during sepsis may be prevented by treatment with a calcium antagonist.

Animals↗
PubMed2001

Intraoperative manometry to assess the esophagogastric junction during laparoscopic fundoplication and myotomy.

SUMMARY: Surgery for gastroesophageal reflux disease and achalasia is performed to alleviate symptoms by improving esophagogastric junction (EGJ) function. Intraoperative manometry was used to evaluate the pressure-length characteristics of the reconstructed EGJ during laparoscopic Nissen fundoplication and laparoscopic Heller myotomy. Intraoperative manometry was performed in 37 consecutive patients undergoing laparoscopic Nissen fundoplication (n = 22) or laparoscopic Heller myotomy (n = 15). Measurements were taken before surgery, after creation of the pneumoperitoneum, after completion of the myotomy in achalasia, and after creation of the fundoplication. Tracings were analyzed for pressure, length, and the integrated pressure-length relation (area under the curve [AUC]). Statistical comparison was made using paired t tests; intraoperative EGJ measurements did not correlate well with preoperative values for either pressure or length. Laparoscopic Nissen fundoplication significantly increased pressure, length, and AUC of the EGJ compared with prefundoplication values. Laparoscopic Heller myotomy significantly decreased EGJ pressure, length, and AUC. Creation of a Toupet fundoplication after myotomy did not significantly increase pressure, length, and AUC of the EGJ compared with postmyotomy values. Intraoperative manometry identified 2 of 15 achalasia patients (13%) with persistent areas of high pressure after initial myotomy that were corrected by extending the myotomy. Intraoperative manometry identifies mechanical changes created during EGJ surgery and may be a useful adjunct to improve outcomes of laparoscopic Nissen fundoplication and laparoscopic Heller myotomy.

Adult↗
PubMed2000

Induction of the stress response in vivo decreases nuclear factor-kappa B activity in jejunal mucosa of endotoxemic mice.

BACKGROUND: Results of previous studies suggest that the stress response protects cells and tissues by regulating proinflammatory mediators. The transcription factor nuclear factor-kappa B (NF-kappa B), normally sequestered in the cytoplasm by its inhibitory protein, I kappa B, regulates many genes involved in inflammatory responses to critical illness. Endotoxemia is associated with increased NF-kappa B activity in intestinal mucosa, but the effect of the stress response on endotoxin-induced NF-kappa B activation in intestinal mucosa is not known. HYPOTHESIS: Induction of the stress response inhibits NF-kappa B DNA binding activity in jejunal mucosa during endotoxemia. METHODS: The stress response was induced in mice by hyperthermia (42 degrees C) or injection with sodium arsenite (10 mg/kg). After 2 to 5 hours, mice were injected with endotoxin (lipopolysaccharide, 12.5 mg/kg) or a corresponding volume of sterile saline. One hour later, jejunal mucosa was harvested for preparation of nuclear and cytoplasmic extracts. RESULTS: Mucosal levels of heat shock protein-72 increased after hyperthermia or treatment with sodium arsenite, consistent with induction of the stress response. The increase in NF-kappa B DNA binding activity and decrease in I kappa B-alpha levels seen after endotoxin injection were inhibited by previous induction of the stress response. CONCLUSION: The protective effects of the stress response in vivo might, at least in part, be due to inhibited NF-kappa B activation.

Animals↗
PubMed2000

Balloon aortic valvotomy through a carotid cutdown in infants with severe aortic stenosis: results of the multi-centric registry.

OBJECTIVES: The purpose of this study was to evaluate the short and intermediate term results of infants who have undergone balloon aortic valvotomy from the carotid arterial approach, and to identify risk factors in those infants who had a poor outcome. METHODS: Between 1988 and 1999, balloon aortic valvotomy was attempted at four centres in 95 infants with severe aortic stenosis. Echocardiographic and hemodynamic data, and outcome, were analysed retrospectively. RESULTS: Valvotomy was accomplished in 92 of the 95 infants, with a median age of 5 days, a range from 0 to 191 days, and weighing 3.4 kg, with a range from 1.0 to 6.5 kg. Major procedural complications occurred in 10 infants. Post-procedural aortic regurgitation was severe in 5 patients. There were 13 early deaths, and 4 late deaths. The period of mean follow-up has been 2.1 years, with a range from 0 to 9.3 years. The actuarial survival at 3 years was 76 +/- 6%. Further interventions were needed in 19 patients, giving a 3-year freedom from reintervention of 67 +/- 6%. The 51 infants who were duct-dependent were further analyzed, and found to have a higher mortality (38%) compared to those infants not dependent on the arterial duct (5%). Risk factors for a poor outcome in the duct-dependent infants were mitral stenosis (p<0.005), a left ventricle which did not form the cardiac apex (p<0.005), and an aortic valve with a diameter of less than 6 mm (p<0.05). CONCLUSIONS: This multi-centric registry shows good results in the intermediate term for treating infants with severe aortic valvar stenosis with balloon valvotomy through a carotid arterial cutdown. Infants dependent on prostaglandin had a worse outcome, especially if they had any of the identified risk factors.

Analysis of Variance↗
PubMed2000

Burn injury upregulates the activity and gene expression of the 20 S proteasome in rat skeletal muscle.

There is evidence that burn injury stimulates ubiquitin-proteasome-dependent protein breakdown in skeletal muscle. In this proteolytic pathway, protein substrates are conjugated to multiple molecules of ubiquitin, whereafter they are recognized, unfolded and degraded by the multicatalytic 26 S protease complex. The 20 S proteasome is the catalytic core of the 26 S protease complex. The influence of burn injury on the expression and activity of the 20 S proteasome has not been reported. We tested the hypothesis that burn injury increases 20 S proteasome activity and the expression of mRNA for the 20 S proteasome subunits RC3 and RC7. Proteolytic activity of isolated 20 S proteasomes, assessed as activity against fluorogenic peptide substrates, was increased in extensor digitorum longus muscles from burned rats. Northern-blot analysis revealed that the expression of mRNA for RC3 and RC7 was increased by 100% and 80% respectively following burn injury. Increased activity and expression of the 20 S proteasome in muscles from burned rats support the concept that burn-induced muscle cachexia is at least, in part, regulated by the ubiquitin-proteasome proteolytic pathway.

Animals↗
PubMed1999

Use of omeprazole in the management of giant duodenal ulcer: results of a prospective study.

BACKGROUND: Giant duodenal ulcer (GDU) is generally thought to require surgical intervention. Proton pump inhibitors have beneficial effects in peptic ulcer disease, but their role in GDU disease is unknown. We examined the use of omeprazole in GDU management. METHODS: Twenty-eight patients were diagnosed with GDU. One patient required immediate operative intervention. The remaining 27 were placed on omeprazole (40 mg daily). When ulcer healing was documented by endoscopy, the patients were placed on oral histamine-2 receptor antagonist therapy. RESULTS: Of the 28 study patients, 20 (71.4%) did not require operative intervention, and 8 (28.6%) required operation for ulcer complications. Of the 15 patients with adherent clot or a visible vessel at initial endoscopy, 7 (46.7%) required operative intervention, as compared with 1 (7.7%) of the 13 patients without a visible vessel or adherent clot. This difference was statistically significant (P < .05). Twenty-three patients underwent antral biopsy and/or enzyme-linked immunosorbent assay for Helicobacter pylori, and 9 (39.1%) had a positive result. CONCLUSIONS: Omeprazole is effective in the treatment of GDU disease. An adherent clot or a visible vessel at endoscopy indicates a higher likelihood of complications requiring operation. The relatively low H pylori infection rate, as compared with other peptic ulcer disease, may indicate a different pathophysiology in GDU.

Adult↗
PubMed1997

Are chest radiographs and electrocardiograms still valuable in evaluating new pediatric patients with heart murmurs or chest pain?

OBJECTIVES: To determine the usefulness of electrocardiography (ECG) and chest radiography (CXR) in evaluation of patients referred to the pediatric cardiologist for the evaluation of heart murmur or chest pain. DESIGN: In this prospective study, 106 consecutive outpatients were categorized with no heart disease, possible heart disease, or definite heart disease based on history and physical examination; they then underwent ECG and CXR. Studies were reviewed and the examining cardiologist could change the diagnosis and order an echocardiogram. SETTING: Academic pediatric cardiology practice. RESULTS: In patients thought to have no heart disease, the diagnosis was changed to definite heart disease in four solely on the basis of abnormal CXR or ECG. In 25 patients thought to have possible heart disease, the diagnosis was changed to no heart disease (7) or definite heart disease (5) after review of the CXR and ECG. All 25 patients diagnosed with definite heart disease had this confirmed by abnormal CXR (2), ECG (3), both abnormal CXR and ECG, or echocardiogram (18). CONCLUSIONS: ECG and CXR helped diagnose heart disease in four patients thought to have no heart disease, helped to rule out lesions in seven patients with possible heart disease, helped diagnose heart disease in five patients thought to have possible heart disease, and helped confirm heart disease in nine patients. In these days of cost containment, routine ECG and CXR continue to be valuable tools for the pediatric cardiologist in evaluation of patients with heart murmurs or chest pain.

Adolescent↗
PubMed1996

Alkynyl phosphates are potent inhibitors of serine enzyme.

Propynyl, hexynyl and t-butylethynyl diethyl phosphates were found to be very powerful covalent inhibitors of serine enzymes. Esterases were inhibited with second-order rate constants of 10(7)-10(8) m(-1) min(-1). Most proteases were inhibited with a rate constant of 10(4)-10(5) M(-1) min(-1). By inhibiting chymotrypsin with (3-14C)-1-propynyl diethyl phosphate, it was established that inhibition was caused by binding of the phosphate group to the enzyme active site.

Aldehyde Dehydrogenase↗
PubMed1995

Increased frequency of deletions in the mitochondrial genome with age of Caenorhabditis elegans.

We have developed a long-extension-PCR strategy which amplifies approximately half of the mitochondrial genome (6.3 kb) of Caenorhabditis elegans using an individual worm as target. We analyzed three strains over their life span to assess the number of detectable deletions in the mitochondrial genome. Two of these strains are wild-type for life span while the third is mutant in the age-1 gene, approximately doubling its maximum life span. At the mean life span in wild-type strains, there was a significant difference between the frequency of deletions detected in the mitochondrial genome compared with the mean number of deletions in young animals. In addition, deletions in the mitochondrial genome occur at a significantly lower rate in age-1 mutants as compared with wild type. We cloned and identified the breakpoints of two deletions and found that one of the deletions had a direct repeat of 8 bp at the breakpoint. This is the largest single study (over 900 individual animals) characterizing the frequency of deletions in the mitochondrial genome as a function of age yet carried out.

Aging↗
PubMed1995

Mechanism-based inactivation of phosphotriesterase by reaction of a critical histidine with a ketene intermediate.

Five alkynyl phosphate esters have been synthesized as probes of the active site structure of phosphotriesterase. These compounds have the potential to be converted by the enzyme to a highly reactive ketene intermediate which can then react with an active site nucleophile causing irreversible inhibition of the enzyme by formation of an inactive covalent adduct. All five compounds completely inactivate enzyme function in less than 15 s at pH 7.0. The partition rations of 1-hexynyl diethyl phosphate (I), 1-propynyl diethyl phosphate (II), 1-hexynyl diphenyl phosphate (III), 1-hexynyl dimethyl phosphate (IV), and ethynyl diethyl phosphate (V) fall in the range between 480 and 1700; thus, all five alkynyl phosphate esters work equally well as inactivators despite the differences in their structures. The rate constants for enzyme inactivation, kinact, are 1.7 s-1 with I, 1.3 s-1 with II, and 0.12 s-1 with IV. They compare well with the kcat for the Co-substituted phosphotriesterase; hence these compounds are good substrates. The stoichiometry of inhibitor bound to protein is 1:1, as determined by inactivation of the enzyme using the radiolabeled compound [3-14C]-1-propynyl diethyl phosphate. Addition of an exogenous nucleophile, azide, did not protect phosphotriesterase from being inactivated by the alkynyl phosphate esters, suggesting that the reactive intermediate produced from the inhibitor is not released from the enzyme surface prior to covalent labeling of the protein. Chemical and spectroscopic evidence suggests that a histidine residue is modified in the inactivation reaction. The inactivated phosphotriesterase can be reactivated by increasing the pH of the protein solution. N-Acylimidazoles are known to be easily hydrolyzed at alkaline pH values.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkynes↗
PubMed1995

Histidine-254 is essential for the inactivation of phosphotriesterase with the alkynyl phosphate esters and diethyl pyrocarbonate.

The alkynyl phosphate ester, 1-hexynyl diethyl phosphate (I), is a mechanism-based inhibitor of phosphotriesterase. It has been previously determined that a histidine residue in the wild-type phosphotriesterase is covalently modified by this compound. In order to identify which of the seven histidine residues in the native enzyme are required for inactivation, the kinetic properties of phosphotriesterase mutants with this suicide substrate were examined in detail. Six of the seven mutants (histidine to asparagine) were rapidly inactivated by I. The mutants H55N, H57N, and H230N also showed partition ratios that were lower than for the wild-type enzyme. The rate of inactivation of H201N was significantly slower than that of wild-type phosphotriesterase. The H254N mutant could not be inactivated; no more than 60% of the initial activity was lost, even at I/E0 ratios of 4000:1. These results suggest that His-254 is essential for the inactivation of phosphotriesterase and is likely to be the primary target in the wild-type enzyme for modification by I. The inactivation of wild-type phosphotriesterase and the seven mutants was also studied using diethyl pyrocarbonate, a histidine selective reagent. The second-order rate constant for the inactivation of wild-type phosphotriesterase was determined to be 1.3 M-1 min-1. The rate constants for the inactivation of the H55N, H57N, H201N, and H230N mutants were larger than for the wild-type enzyme. Thus, it appears that when these histidine residues are replaced by asparagine, other histidine residues in the active site become more susceptible to modification, resulting in a faster rate of inactivation. The mutant H254N was not inactivated in the presence of DEPC.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkynes↗
PubMed1992

Long-term results of survivors of surgical valvotomy for severe aortic stenosis in early infancy.

Long-term morbidity and mortality were evaluated in the 21 survivors of a cohort of 51 consecutive infants with severe aortic valve stenosis who underwent surgical treatment in the first 3 months of life during the period from 1958 to 1988. The 21 early survivors have been followed up from 3 to 27 years (median 7.5 years). There have been two late deaths: one at age 13 year from bacterial endocarditis and the other at age 14 years after dislodgment of a prosthetic valve. The calculated 10-year actuarial survival for this group is 100%, with a 15-year actuarial survival of 75% (standard error 15%). Seven repeat operations have been performed in six patients: Three had persistent stenosis and a repeat valvotomy was performed in two of them, aged 2 years and 15 years. The other underwent placement of a conduit from the left ventricle to the descending aorta at 2 years of age. Replacement of the aortic valve has been performed in four patients because of severe valvular insufficiency 13 to 27 years after the initial operation. One of these had required a repeat valvotomy at the age of 15 years. The calculated actuarial freedom from reoperation at 10 years is 90% (standard error 6%) and at 15 years, 67% (standard error 15%). Aortic insufficiency was progressive throughout the period of follow-up. No patient had more than moderate aortic insufficiency 3 to 5 years after the initial valvotomy, whereas aortic insufficiency was severe in five of the eight patients followed up for 11 or more years. Progression of aortic insufficiency and the need for reoperation were not related to the age at initial valvotomy. Survivors of surgical aortic valvotomy in early infancy have a relatively good long-term prognosis and a high freedom from reoperation in the period leading to adolescence. Aortic insufficiency in these patients is progressive, and valve replacement eventually may be required.

Actuarial Analysis↗
PubMed1991

Acute myocarditis simulating myocardial infarction in a child.

Pediatric chest pain usually occurs in benign conditions. However, this case portrays the dramatic electrocardiographic appearance of acute myocardial ischemia in a boy with biopsy-proven myocarditis who had only mild chest pain. This underscores the need for eliciting a detailed history when evaluating a patient with chest pain. If the pain cannot be clearly attributed to chest wall phenomena, or if there are historical or physical findings suggestive of an arrhythmia or angina, then further investigation with a chest radiograph and a 12-lead electrocardiogram is recommended. Myocarditis must be considered in the differential diagnosis of any child whose electrocardiogram is indistinguishable from an acute myocardial infarction. Finally, endomyocardial biopsy allows early diagnosis and institution of therapy, which may have beneficial effect on decreasing morbidity and mortality. Further follow-up and research is still needed to evaluate the effect of early treatment of myocarditis on long-term myocardial function and the development of chronic cardiomyopathy.

Biopsy↗
PubMed1990

Carotid artery approach for balloon dilation of aortic valve stenosis in the neonate: a preliminary report.

Balloon valvuloplasty in neonates with severe aortic valve stenosis is limited by difficulties in catheter manipulation around the arch and across the valve and by the risk of femoral artery complications. A right common carotid artery cutdown was utilized for balloon aortic valvuloplasty in five neonates 1 to 20 days of age, weighing 3.1 to 3.9 kg. Standard balloon valvuloplasty was performed through a 6F sheath inserted in the right carotid artery. The arteriotomy was repaired at the end of the procedure. Mean left ventricular systolic pressure was reduced from 142 to 97 mm Hg, with a decrease in mean peak systolic pressure gradient from 76 to 33 mm Hg. Only one patient developed mild aortic regurgitation. One patient with a hypoplastic left ventricle died, and one patient required open valvotomy. All four survivors have a normal carotid pulse and no neurologic sequelae. Two of these patients required repeat balloon dilation to treat residual aortic valve stenosis at 8 and 10 months of age, respectively. Balloon valvuloplasty using a carotid artery approach is feasible and was safe in five neonates with severe aortic valve stenosis.

Aortic Valve↗
PubMed1989

Extracorporeal membrane oxygenation for postcardiotomy cardiogenic shock in children.

Size limitations and technical barriers prohibit the use of many conventional mechanical circulatory support systems for postcardiotomy ventricular dysfunction in pediatric populations. Extracorporeal membrane oxygenation (ECMO), frequently used to treat neonatal respiratory failure, can provide cardiac support and is effective treatment of postoperative myocardial failure in children. From 1981 to 1987, 10 patients aged 2 days to 5 years were maintained on ECMO for 15 to 144 hours (mean duration, 92 +/- 16 hours) after cardiotomy. Operative procedures included repair of tetralogy of Fallot (2 patients), closure of a ventricular septal defect (2), the Senning procedure for transposition of the great arteries (1 patient), repair of interrupted aortic arch with closure of a ventricular septal defect (1), repair of a partial atrioventricular septal defect (2), closure of a ventricular septal defect with excision of an anomalous muscle bundle (1), and the Fontan procedure (1). Venoarterial ECMO was established in all 10 children. Six patients underwent transthoracic right atrium-ascending aorta cannulation, 3 had right internal jugular vein-right common carotid artery cannulation through a cervical incision, and 1 had right internal jugular vein-left axillary artery cannulation. Eight of the 10 patients were successfully weaned from ECMO, and 7 are long-term survivors. There were 3 deaths; 1 was caused by cardiac and acute renal failure complicated by sepsis two days after decannulation, another occurred 19 days after atrioventricular septal defect repair, and 1 was caused by massive pulmonary hemorrhage. Major hemorrhage developed in 3 patients while on ECMO; 2 required premature decannulation for mediastinal bleeding from operative sites and ultimately survived, and 1 died of respiratory failure as a result of endobronchial bleeding. We conclude that the use of ECMO in pediatric populations for transient postoperative ventricular dysfunction improves survival with limited overall morbidity.

Child, Preschool↗