The St. Jude Medical cardiac valve in infants and children: role of anticoagulant therapy.

The experience at the University of Colorado with the St. Jude Medical cardiac valve was reviewed to determine the feasibility of placing this prosthesis in children and the role of anticoagulation. A St. Jude Medical cardiac valve was placed in 33 patients ranging in age from 2.5 months to 17 years. Seven patients were less than 1 year of age. Nineteen valves were placed in the aortic position in patients aged 5 months to 17 years (mean 9.5 years). Five patients had valve replacement only, 13 had concomitant aortoventriculoplasty and 1 a Manouguian procedure. Indications for anulus enlarging procedures were recurrent subaortic stenosis or inability to place an adult-sized valve in the native aortic anulus, or both. There were no early or late deaths. Fourteen valves were placed in the mitral position. They were anular positioned in 6 patients aged 6 months to 16 years and supraanular positioned in 8 patients aged 2.5 months to 2 years. There were no deaths with the anular positioned replacements and seven deaths (two early and five late) with the supraanular positioned replacements. Four of the five late deaths were associated with marked pre- and postoperative left ventricular dysfunction. The follow-up time was 784 patient-months in 31 long-term survivors. Anticoagulation was achieved with warfarin, usually in combination with sulfinpyrazone, dipyridamole or aspirin. There were four episodes of thromboembolism, three occurring in patients with suboptimal anticoagulation, and one in a patient lost to follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)

Histone positions within the nucleosome using platinum labeling and the scanning transmission electron microscope.

An approach to studying the organization of macromolecular complexes using heavy-atom labeling has been developed and applied to the problem of determining the positions of the histone proteins within the nucleosome. The approach is based on the capability of the scanning transmission electron microscope to image heavy atoms. Nucleosomes containing histones labeled with heavy atoms were prepared by lysine modification of selected histones with methyl (methylthio)acetimidate, followed by reconstitution of the modified histones into nucleosomes, and reaction of the reconstituted nucleosomes with chloroglycyl-1-methioninatoplatinum (II). Micrographs of the platinum-labeled nucleosomes were obtained using the scanning transmission electron microscope, and analyzed using both computer and manual techniques. The results of the analysis were 24 A resolution maps of the distribution of high electron scattering density picture elements (representative of platinum atoms) indicating the position of each histone. The significance of those results and the general applicability of the platinum-labeling techniques are discussed. Finally, a description of the histone positions within the nucleosomes is presented and discussed in relation to the current literature on nucleosome structure.

Distribution of mass within native thick filaments of vertebrate skeletal muscle.

The distribution of mass within the vertebrate skeletal thick filament has been determined by scanning transmission electron microscopy. Thick and thin filaments from fresh rabbit muscle were mixed with tobacco mosaic virus (TMV), fixed with formaldehyde, dried onto thin carbon films and viewed in a computer-linked microscope. Electron scattering data from both TMV and thick filaments were analysed with reference to the long axis of the particles so that the distribution of mass within the particles could be determined. While TMV appeared to be a uniform rod at the resolution employed (4.3 nm), the thick filament was clearly differentiated along its length. M-line remnants at the centre of the filament were flanked by regions of low mass per unit length, corresponding to the bare zone of the filament, and then by the more massive cross-bridge regions. The mass per unit length was approximately constant through most of the cross-bridge zone and declined at the filament tips, in a manner consistent with a constant number of myosin molecules per 14.3 nm interval (crown) throughout the cross-bridge zone. Fourier analysis of the data failed to detect the expected 43 nm periodicity of C-protein. The total mass of the thick filament was 184 Mdalton (s.e.m., 1.6 X 10(6); n = 70). The mass of adhering M-line proteins was highly variable but, on average, was about 4 Mdalton. The total mass of the filament and the mass distribution in the cross-bridge zone are consistent with three myosin molecules per crown.

Pulmonary vascular response to oxygen in infants with severe bronchopulmonary dysplasia.

The cardiac catheterization data of six infants with bronchopulmonary dysplasia (BPD) were reviewed to examine the responsiveness of their pulmonary vascular beds to changes in oxygen tension. The infants were studied because of slow recovery from their oxygen requirements and clinical evidence of persistent pulmonary hypertension. All were receiving home oxygen therapy and had abnormal chest radiographs and right ventricular hypertrophy by ECG at the time of catheterization (mean age, 25 months). All infants had mean pulmonary artery pressure greater than 25 mm Hg in room air, with a mean of 48 mm Hg. All decreased mean pulmonary artery pressure by at least 10 mm Hg when placed in high levels of inspired oxygen (FiO2 greater than 80), with a mean pulmonary artery pressure of 25 mm Hg. This represented a significant decrease in mean pulmonary artery pressure from room air pressures (P less than .005). Mean pulmonary artery pressure was also measured in three infants who were breathing supplemental oxygen by nasal cannula at flow rates similar to levels used for outpatient therapy. Most of the reduction in mean pulmonary artery pressure that occurred at high FiO2 occurred at these lower flow rates of supplemental oxygen. It is concluded that infants with bronchopulmonary dysplasia who have pulmonary hypertension generally have reactive pulmonary vascular beds, responsive to supplemental oxygen. Continuous oxygen therapy by nasal cannula may be useful in the treatment of pulmonary hypertension associated with bronchopulmonary dysplasia.

Outbreak of Kawasaki syndrome in Denver, Colorado: association with rug and carpet cleaning.

Between October 1984 and January 1985, the largest outbreak of Kawasaki syndrome reported to date in the continental United States (62 cases) occurred in the Front Range of the Rocky Mountains, extending from Colorado Springs, Colorado, to Cheyenne, Wyoming. Fifty-two (84%) of these Kawasaki syndrome patients lived in the Denver metropolitan area. A case-control study revealed that 16 (62%) of 26 Kawasaki syndrome patients compared with 10 (20%) of 49 matched control subjects had a history of exposure to shampooed (19%) or spot-cleaned (81%) rugs or carpets within 30 days of the Kawasaki syndrome onset date (odds ratio = 5, P less than .01). The time of exposure to shampooed or spot-cleaned rugs or carpets for 9 of 10 Kawasaki syndrome patients who had a single exposure and for all 6 Kawasaki syndrome patients who had multiple exposures were clustered within an interval 13 to 30 days before the onset of illness. Although the reason for this unusually large outbreak remains obscure, it is the third in which a statistically significant association between Kawasaki syndrome and rug or carpet cleaning has been found.

Hemodynamic effects of ketamine, hypoxia and hyperoxia in children with surgically treated congenital heart disease residing greater than or equal to 1,200 meters above sea level.

Little data are available on the hemodynamic effects of premedications and anesthetic agents on infants and children. Ketamine is the most frequently used anesthetic agent for cardiac catheterization procedures in pediatric patients with congenital heart disease. Previous reports both suggest and deny ketamine's pulmonary vasoreactive effects. Since the advent of sophisticated noninvasive equipment, one of the few indications for cardiac catheterization is to obtain accurate pressure data. If ketamine alters pulmonary vascular resistance, it would negate the primary reason for the procedure. Because the patient population studied herein resides greater than or equal to 1,200 meters above sea level, concerns about pharmacologic effects on pulmonary vascular resistance are enhanced. Simultaneous pulmonary artery and aortic pressures, thermodilution cardiac outputs, and blood gases were measured in room air (16% oxygen) and with ketamine infusion in 14 patients at cardiac catheterization. Reaction to hypoxia identified 3 groups: normal, intermediate and hyperresponders. The normal responders had normal resistance ratios (0.11) in room air and had little resistance ratio response to hypoxia (+0.02), hyperoxia (-0.03) or ketamine (+0.01). The intermediate responders had a slightly higher but normal resistance ratio (0.20) in room air, and a moderate reaction to hypoxia (+0.13), hyperoxia (-0.08) and ketamine (+0.11). The hyperresponders had an elevated resistance ratio (0.42) in room air and a striking reaction to hypoxia (+0.65), hyperoxia (-0.17) and ketamine (+0.49). Hypoxia and ketamine have a greater effect on resistance ratio than hypoxia alone in patients with reactive pulmonary vascular beds. Ketamine should not be used in children undergoing procedures to establish operability based on pulmonary vascular resistance or pulmonary vascular reactivity.

Extended aortic root replacement with aortic allografts.

Complex left ventricular outflow tract obstruction after operation for subaortic stenosis or with hypoplastic aortic anulus remains a challenge for pediatric cardiac surgeons. We have recently applied a new technique of extended aortic root replacement using a cryopreserved aortic allograft to treat two patients who had previously been operated on for subaortic stenosis and a third who had aortic stenosis with a hypoplastic aortic anulus. This new procedure combines the concept of aortoventriculoplasty with aortic root replacement and coronary artery reimplantation. The valved aortic homograft is used in place of an aortic valve prosthesis and the attached anterior mitral leaflet augments the interventricular septum to relieve the subvalvular left ventricular outflow tract obstruction. The coronary ostia are then reimplanted into the allograft and an anastomosis between the distal graft and the ascending aorta is completed. Allograft aortic tissue is then used to patch the right ventricular outflow tract. One patient had aortic stenosis with annular hypoplasia and did well after extended root replacement. Two patients had previous operations for subaortic stenosis before undergoing extended aortic root replacement. One required mediastinal exploration and drainage at 2 weeks for Serratia marcescens mediastinitis and bacteremia, but uncomplicated recovery followed. The other patient had complete heart block for 2 days, but normal sinus rhythm resumed and convalescence was benign. This modified technique with the aortic allograft was very helpful in treating these difficult problems, and the lack of mortality, limited morbidity, and good functional results are encouraging.

Aortoventriculoplasty in children.

Aortoventriculoplasty was performed in 16 children between July, 1980, and July, 1984. Indications for the procedure were 1) aortic stenosis or insufficiency, or both, necessitating replacement of an aortic valve whose anulus would not accept a 19 mm diameter valve, (2) replacement of a small valve prosthesis, or (3) recurrent tunnel subaortic stenosis. Patients were 5 months to 17 years old at operation, 14 had previous repairs, and four had prior aortic valve replacement. There were 13 long-term survivors followed up for 14 to 38 months; 12 are asymptomatic with normal exercise tolerance. Three had residual ventricular septal defects, two requiring repair. All patients were given warfarin with or without antiplatelet agents. There have been no thromboembolic episodes and no hemorrhagic complications. Aortoventriculoplasty is well tolerated in children and appears to be a viable surgical option in the management of young patients with a hypoplastic left ventricular outflow tract.

Evolution of the management of anomalous left coronary artery: a new surgical approach.

Twelve patients with anomalous left coronary artery (LCA) from the pulmonary artery were treated surgically. Mean age was 13 months and mean weight, 7.7 kg. One of the following techniques was used in 8 patients: suture obliteration of the coronary orifice, ligation of the anomalous LCA and grafting of the internal mammary artery to the distal LCA, aortic reimplantation of the anomalous LCA, creation of an aortopulmonary window, and direct anastomosis to the right subclavian artery. In 4 patients, a new technique to establish a two-coronary artery system involved tube extension of the anomalous LCA with pulmonary artery wall and then anastomosis to the right subclavian artery using cardiopulmonary by-pass without aortic cross-clamping. There were two hospital deaths (17%) and one late death. The condition of the 9 long-term survivors was improved at late follow-up. Postoperative assessment showed smaller Q wave on the electrocardiogram, reduced cardiac size, and good left ventricular function. All patients in whom the repair was done using the new technique were free from postoperative cardiac complications, had shortened hospital stays, and were alive with a patent two-coronary artery system at late follow-up. We believe this approach is a safer method for establishing a two-coronary artery system in infants and small children with an anomalous LCA arising from the pulmonary artery.

Johns Hopkins University, Baltimore, Maryland.

The STEM can be used in one of three modes: 1) to image individual atoms; 2) to measure mass or molecular weight; 3) to collect electron energy loss spectra or x-ray fluorescence data. Heavy atom imaging is used to identify chemical groups in a molecule or macromolecules in an assembly. Specific labels have been developed for bases in nucleic acids. These permit localization of bound proteins on single strand nucleic acids. Pt(gly-L-met)Cl is a specific label for methionine residues of proteins as shown with the SLS aggregate of collagen. Lysine can be labeled as well if first methyl (methyl-thio-acetimidate) is coupled. This labeling procedure permits the localization of individual histones within a nucleosome. Mass determination can be used to answer crucial questions about biological assemblies. This is demonstrated by examples from muscle structure.

High-resolution scanning transmission electron microscope at Johns Hopkins.

The scanning transmission electron microscope constructed at Johns Hopkins follows the general layout of the first instrument at the University of Chicago. It is currently operating at 50 kV with a resolution of about 3 A. Its detector scheme consists of scintillation crystals coupled to photomultipliers in such a way as to eliminate introduction of unnecessary statistical noise. A unique alignment scheme utilizes the spherical aberration of the objective lens.

Inducing tricuspid regurgitation as palliation.

We describe a technique for palliative decompression of the hypertensive right ventricle seen in pulmonary atresia with intact ventricular septum (PAIVS), utilizing a bioptome catheter for partial tricuspid avulsion.

Increased lung vasoreactivity in children from Leadville, Colorado, after recovery from high-altitude pulmonary edema.

Cardiac catheterization was performed on seven children after recovery from high-altitude pulmonary edema. All were life-long residents at elevations above 10,000 feet. Three of the seven had developed pulmonary edema without antecedent travel to low altitude but had an upper respiratory infection. Response of pulmonary arterial pressure to 16% inspired oxygen in all seven was compared with that in six well children who resided at a similar altitude and had no history of high-altitude pulmonary edema. With hypoxia the susceptible patients had a greater mean pulmonary arterial pressure (56.3 +/- 23.8) than the nonsusceptible children (18.8 +/- 3.9, p less than .05). Comparison with historical hemodynamic responses in children at high altitudes showed a similar greater mean pulmonary arterial pressure in the susceptible children. Thus, in children from high altitudes, increased pulmonary vasoreactivity to hypoxia may play a role in the pathogenesis of high-altitude pulmonary edema. The development of pulmonary edema in high-altitude residents with upper respiratory infections and no antecedent low-altitude journey is consistent with the presence of other factors such as inflammation, which may play a role in the pathogenesis of the edema. The finding of right ventricular hypertrophy on an electrocardiogram in children from high altitudes may be predictive of their susceptibility to high-altitude pulmonary edema.

Spontaneous chylothorax in Noonan syndrome. Treatment with prednisone.

OBJECTIVE: To describe a case of spontaneous chylothorax in a child with Noonan syndrome successfully treated with prednisone. DESIGN: Case report. SETTING: A pediatric cardiology referral center for the Rocky Mountain region. PATIENT: An 18-month-old girl with Noonan's syndrome, pulmonary stenosis, and hypertrophic cardiomyopathy who presented with spontaneous chylothorax. INTERVENTIONS: The child's chylothorax did not respond to thoracic duct ligation, tetracycline pleurodesis, and pleurectomy during a 2-month period. A low-fat diet was helpful but did not eliminate the problem. Prednisone was started orally at 1 mg/kg per dose twice daily and slowly tapered during 3 months. The chylothorax did not recur during 8 months of follow-up. CONCLUSIONS: Prednisone may be useful in the treatment of chylothorax in Noonan syndrome. A controlled clinical trial would be helpful but would be difficult in such a rare complication of an uncommon syndrome.

Chronic posttraumatic thoracic aortic aneurysm presenting with dysphagia.

Chronic posttraumatic thoracic aortic aneurysms are rare. The natural history of these aneurysms is symptomatic enlargement. Herein is reported a chronic posttraumatic thoracic aortic aneurysm that became symptomatic by producing extrinsic compression of the esophagus. Despite the chronic nature of these aneurysms they should be repaired when found.