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Biomedical subjects

J W Wiggins

Publications and source records attributed to J W Wiggins.

33 records · Page 2Linked to original sources

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.

Adolescent↗

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.

Actin Cytoskeleton↗

Echocardiographic diagnosis and intravenous digoxin management of fetal tachyarrhythmias and congestive heart failure.

Fetal echocardiography now affords an accurate clinical diagnosis of nonimmune fetal hydrops secondary to fetal tachyarrhythmias and/or certain types of congenital heart disease. Individual case reports of the treatment of tachyarrhythmias have been reported that use various drugs, including digoxin, propranolol hydrochloride, procainamide hydrochloride, and digoxin plus verapamil hydrochloride. We found no report of intrauterine treatment of congestive heart failure due to congenital heart disease with sinus rhythm. The seven cases presented herein include five cases of isolated supraventricular tachycardia, one with supraventricular tachycardia and myocardial tumors, and one of congenital heart disease with congestive heart failure. Maternal treatment with digoxin converted tachyarrhythmia to sinus rhythm in all six fetuses, and resolved the hydrops in the fetus with congenital heart disease. Premature delivery was avoided in five of the seven cases with favorable outcome in six of the cases. In five mothers who were given oral digitalization, the fetuses had delayed (three to 35 days) response to therapy. Two mothers were treated intravenously and the fetus responded to therapy in less than 24 hours. Because of problems possibly related to poor absorption and/or rapid clearance of digoxin, the intravenous route of administration should be used as the best way to achieve adequate therapeutic levels in the fetus.

Atrioventricular Node↗

Clinical spectrum of Kawasaki disease in infants younger than 6 months of age.

We report an unselected series of eight patients younger than 6 months of age with Kawasaki disease evaluated between January 1982 and May 1984. The incidence of coronary artery aneurysms (six patients) and the mortality (two patients) were unusually high in this small series. Because of the confusing clinical presentation in three patients, diagnosis was delayed until pathologic or echocardiographic evidence of coronary vasculitis or aneurysm was discovered. The currently accepted clinical criteria for Kawasaki disease may not always identify patients with the pathologic findings of the syndrome who are younger than 6 months of age. The diagnosis of Kawasaki disease and echocardiographic evaluation of the coronary arteries should be considered in young infants with prolonged fever of unknown origin.

Aspirin↗

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.

Adolescent↗

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.

Altitude↗

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.

Bronchopulmonary Dysplasia↗

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.

Affinity Labels↗

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.

Amino Acids↗

Infant coarctation of the aorta. Alternatives to subclavian flap repair.

Three cases of infant coarctation that could not be repaired by subclavian flap aortoplasty were repaired by alternative techniques. The principles of subclavian flap were considered and its major advantages preserved: in one case by using a common carotid artery flap and in two cases by constructing a free subclavian artery patch graft. Both of these alternatives worked well and should be considered for repair of infant coarctation when the anatomy is unsuitable for subclavian flap aortoplasty.

Aorta↗

Location of platinum binding sites on bacteriorhodopsin by electron diffraction.

A platinum-containing derivative of bacteriorhodopsin has been prepared by treating purple membranes with glycyl-L-methionatoplatinum. Low-dose electron diffraction was used to identify Pt binding sites in the 5.6 A resolution reconstruction of the bacteriorhodopsin unit cell in projection. This is a necessary first step in the use of the Pt derivative for identifying the parts of the amino acid sequence corresponding to the alpha helices in the bacteriorhodopsin structure and for obtaining phases for reflections out to 3.5 A resolution by the method of heavy-atom isomorphous replacement. The largest peak in a Fourier difference map between platinum-labeled and native purple membrane is larger than the spurious features expected to arise from errors in measurements of diffraction intensities.

Journal Article↗

The use of papaverine in arterial sheaths to prevent loss of femoral artery pulse in pediatric cardiac catheterization.

This study evaluated the efficacy of intraarterial papaverine infusion after pediatric cardiac catheterization in reducing the incidence of lost pulse. This study was conducted at a teaching pediatric hospital and was designed as a randomized, prospective, double-blind, placebo-controlled study. Patients were children 5 years old or less undergoing antegrade and retrograde heart catheterization. The intervention used was an intraarterial infusion of placebo or 1.5 mg/kg papaverine after catheterization. Bilateral femoral artery ultrasound study was performed pre- and postcatheterization, including two-dimensional, color, spectral, and pulsatility index analysis. Outcome measures included clinical loss of pulse, ultrasound findings, plus other clinical factors. Fifty-six patients participated in the study (28 per group). Six patients clinically lost the pulse in the catheterized arteries [four in the papaverine and two in the placebo groups (p > 0.64)]. Clinical loss of pulse correlated with diminished pulsatility index (p < 0.035). The use of papaverine did not prevent decreased pulse or pulsatility index (p > 0.79). Increased arterial time was the only clinical factor associated with lost pulse (p < 0.0004). Pulsatility index <3.34 correlated with loss of pulse in the catheterized artery. The results indicated that intraarterial papaverine infusion after femoral artery catheterization does not prevent loss of pulse in the catheterized artery, and decreased pulsatility index correlates with diminished pulse and represents a good noninvasive method of evaluating femoral artery patency and flow.

Cardiac Catheterization↗