Theadis R. Wells

Bronchial anatomy in syndromes with abnormal visceral situs, abnormal spleen and congenital heart disease

Abstract The bronchial anatomy of a series of patients with congenital heart disease plus either or both abnormal visceral situs and abnormal spleen (absent, multiple, bifid or with unusually large accessory spleen or spleens) was studied by dissection and bronchographic methods. The results suggest that 5, and perhaps 6, syndromes can be delineated: (1) asplenia (Ivemark syndrome), characterized by bilateral eparterial bronchi (bilateral right or 3-lobed lung) and abnormal visceral situs; (2) polysplenia, characterized by bilateral hyparterial bronchi (bilateral left or 2-lobed lung) and abnormal visceral situs; (3) M-anisosplenia (third syndrome), characterized by bilateral eparterial bronchi and a relatively normal visceral situs; (4) F-anisosplenia (fourth syndrome), characterized by bilateral hyparterial bronchi with a visceral situs that is less abnormal than that observed in asplenia or polysplenia; (5) situs inversus, characterized by reversed bronchial pattern (eparterial bronchus on left and hyparterial on right) and reversed visceral situs; and (6) a group characterized by total anomalous pulmonary venous return, normal visceral situs, normal bronchial pattern, and 1 or more accessory spleens. Typical cardiac malformations were demonstrated in each of these syndromes. The results suggest that air or contrast bronchography can be of value in assessing patients with congenital heart disease plus abnormal visceral situs.

Studies on isolated human skeletal muscle fibers, including a proposed pattern of nuclear distribution and a concept of nuclear territories.

Abstract Studies of human skeletal muscle fibers from tissue specimens isolated by supersonic cavitation, employing a Willens Polytron, show that the number of nuclei per millimeter, the surface area of fiber per nucleus, and the cytoplasmic volume per nucleus increase with fiber diameter, for fibers from the same muscle, from muscle to muscle, and from patient to patient. Skeletal muscle fibers from patients with Pompes disease, muscular dystrophy (both autosomal and sex linked recessive juvenile forms), Riley-Day central autonomic dysfunction, and cardiomyopathy with skeletal muscle weakness show increased N/mm. and decreased A/N and V/N values, whereas fibers from patients with the Down syndrome show low N/mm. and high A/N and V/N values. Possibly abnormal fiber values were also observed in familial cerebellar atrophy with mental retardation, in 18 trisomy, Jansky-Bielschowsky disease, and ataxia-telangiectasia. Skeletal muscle fibers from autosomal recessive (“limb girdle”) muscular dystrophy show segmental, and those from Duchennes dystrophy diffuse, hypernucleation. In Pompes disease, acid mucopolysaccharide occurs in discrete “packages” in skeletal muscle, muscles of respiration showing less acid mucopolysaccharide than others. Evidence that the nuclei of skeletal muscle fibers are arranged in a pattern based on a hexagonal array, such that the fibers are covered by nuclear territories of relatively uniform size and shape, is presented, models of such architecture are presented, and possible biochemical implications of nuclear territories are discussed. Evidence that division of fiber nuclei is amitotic is presented. The concept that nuclear rows or chains in skeletal muscle fibers are nuclear clones is proposed, and possible biochemical implications of this arrangement are also discussed.

Time Course of the Intrahepatic Lesion of Extrahepatic Biliary Atresia: A Morphometric Study

The time course of the intrahepatic lesions of untreated extrahepatic biliary atresia was evaluated by morphometric analysis of 49 specimens from 27 patients. The data show an early phase of rapid bile ductular proliferation, with peak in this material at 205 days, followed by rapid duct regression to approximately 400 days, and slower progressive intrahepatic duct loss thereafter. The ratio of ducts to connective tissue in portal tracts follows a similar course. Connective tissue in portal tracts rises on a slower course and continues to increase after maximum duct regression is reached, so the ratio of parenchyma to fibrous septa falls over the later course of the process. Although duct and connective tissue proliferation in hepatic portal tracts is associated in many liver diseases, the data of this study demonstrate dissociability of the relationships, with the fibrosis in the later stages of the intrahepatic process in extrahepatic biliary atresia apparently neither responsive to nor inducing biliary ductular proliferation.

Short Trachea, with Reduced Number of Cartilage Rings-A Hitherto Unrecognized Feature of Digeorge Syndrome

Adequate tracheas from 6 of 14 patients with DiGeorge syndrome (2 complete and 4 partial forms) were available for tracheal ring study. The number of tracheal rings in these patients was significantly low (mean +/- SD 14.7 +/- 1.4). This is consistent with an effect of deficient blood supply to the fetal cervical region, a mechanism that has been proposed to explain the defective development of thymus and parathyroid glands in DiGeorge syndrome. To our knowledge this lesion has not been described as one of the malformations found in the syndrome. In 8 of 14 (57%) patients with DiGeorge syndrome, common origin of the carotid arteries was found, and 4 of these 8 patients showed minor tracheal compression. These findings support the proposal that abnormal blood supply to the region of the third and fourth pharyngeal arches may play a role in the pathogenesis of DiGeorge syndrome.

Incidence of short trachea in patients with myelomeningocele

Short trachea, typically due to reduced tracheal cartilage ring number, produces high tracheal bifurcation which can be demonstrated in radiographs with evaluable air bronchograms. Accidental bronchial intubation with sequelae has been reported in short trachea patients who have tracheal intubation. Short trachea is associated with a number of syndromes, including DiGeorge anomaly and several types of congenital heart disease and skeletal dysplasias. Review of chest radiographs of 87 patients with myelomeningocele revealed that 31 (36%) had short tracheas. Two patients had a total of 3 episodes of bronchial intubation. This degree of association of short trachea with myelomeningocele, the frequency of myelomeningocele, and the number of surgical procedures performed on many such patients suggest that special attention to the short trachea is warranted in myelomeningocele patients because of the risk of accidental bronchial intubation and subsequent sequelae. Twelve (14%) of the myelomeningocele patients lacked radiographic evidence of the presence of twelfth ribs and 11 (13%) had hypoplasia of the twelfth ribs.

Ossification centre of the hyoid bone in DiGeorge syndrome and tetralogy of Fallot

The incidence of radiographic visibility of the ossification centre of the body of the hyoid bone in radiographs taken during the first month of life was analysed for 34 autopsied infants: 16 with DiGeorge syndrome (DGS), 14 with tetralogy of Fallot (TOF), four with interrupted aortic arch (IAA) and a further 13, surviving infants with non-DGS TOF or non-DGS IAA. The incidence of visible hyoid ossification centre (HOC) was 75.7% in a control series of infants with neither congenital heart disease (CHD) nor DGS. Autopsied patients with DGS, TOF without DGS, and IAA without DGS showed a significantly low incidence of visible HOC. Infants with TOF (and possibly those with IAA) who did not have DGS and who did not die during infancy showed a normal incidence of visible HOC in radiographs taken during the first post-natal month. Radiological visibility of the HOC in the first post-natal month appears useful in the diagnosis of DGS and forms of CHD often seen in association with DGS and in assessing prognosis of neonates with certain types of CHD.

The Renal Lesion of Congenital Hepatic Fibrosis: Pathologic and Morphometry Analysis, with Comparison to the Renal Lesion of Infantile Polycystic Disease

The renal lesion of congenital hepatic fibrosis (CHF = Blyth and Ockendens juvenile polycystic disease of liver and kidneys) was analyzed from 6 specimens from patients aged 3 3/12 to 19 3/12 years and compared with that of 5 patients with infantile polycystic disease (IPCD) aged 6 months to 14 4/12 years. Pathologic, microdissection, injection, and morphometric studies show that the predominantly medullary cystic lesion of CHF shows different distribution in medullary, cortico-medullary, and cortical zones of kidney from the lesion of IPCD, and shows a different time course, from early life to renal insufficiency, from that of IPCD. The renal cysts in CHF affect deep or central collecting tubules, in contrast to the involvement of more peripheral orders of collecting tubules in IPCD. Papillary pore counts, performed for 1 patient, gave significantly low values, in contrast to normal values reported for IPCD. The findings support the previously published conclusion, based on differences in the hepatic lesions of the two conditions, that CHF and IPCD are difference diseases, rather than different permissible manifestations of a single disease.

BRANCHING PATTERNS OF RIGHT PULMONARY ARTERY IN CARDIOVASCULAR ANOMALIES

The branch of the right pulmonary artery (RPA) to the upper lobe of the right lung (RUL), the truncus anterior of the RPA, and the pars anterior of the left pulmonary artery, which supplies the left upper lung lobe (LUL), were demonstrated by both dissection of postmortem specimens and angiography for 20 infants and children, by angiography only for 57, and by specimen dissection only for 59 (total 136). In posteroanterior angiograms, the RUL artery branches from the RPA near the right lateral border of the vertebral column, while the LUL artery or arteries arise more laterally, near the left midclavicular plane. This pattern is reversed in situs inversus (eight patients studied). Thirty-nine patients in other categories of congenital cardiovascular disease showed an abnormal RUL or LUL arterial pattern, including pulmonary isomerism, right lung type (RUL artery pattern present bilaterally, 12 patients); pulmonary isomerism, left lung type (RUL artery pattern absent bilaterally, 11 patients); scimitar syndrome (RUL artery pattern normal, 1 patient; absent bilaterally, 4 patients); and left pulmonary artery sling (RUL artery normal, one; hypoplastic, one; absent, two patients). Five patients with tetralogy of Fallot (TOF) with right aortic arch (RAA) and 1 of 15 with RAA not TOF or situs inversus showed a relatively large RUL artery arising more laterally than usual. Three of six patients with double outlet right ventricle had the LUL artery larger than usual plus two accessory RUL arteries, and one patient with crossed pulmonary arteries showed a similar pattern. Two patients with single ventricle had an RUL artery of normal pattern although the RUL bronchus was absent, and one patient with single ventricle and situs inversus had a comparable pattern in the left lung. The ease of demonstration of the right and left upper lobe branches of the pulmonary artery by dissection or angiocardiography warrants greater attention to their patterns in patients with congenital cardiovascular disease. Dissociation of upper lobe bronchial and vascular patterns is unusual and may also be of diagnostic value.

Abnormal growth of the thyroid cartilage in the DiGeorge syndrome.

Larynges from 17 patients with DiGeorge syndrome (DGS) and from 14 patients with tetralogy of Fallot (TOF) (11 non-DGS and 3 possible but unproven DGS) were dissected, measured, and compared to a control population of comparable body length. The patients with DGS and the 3 patients with TOF suspected of having DGS showed the following: small thyroid cartilages with increased anterior angle, abnormally short superior cornua, low ratio of mean superior cornual length to distance between superior cornual tips, and delayed time of maximal rate of increase in superior cornual length relative to increase in body length. The hypoplasia, delayed maximal growth rate and persistent fetal shape of the thyroid cartilage (predominantly a derivative of the fourth branchial arch) in DGS, indicates that the causative process in the syndrome affects not only the third and fourth branchial pouches, but also, by a contiguous field defect, other derivatives than great vessels of the fourth-sixth branchial arches.

Microdissection Study of the Myentric Plexus in Acardia, Ataxia-telangiectasia, Cystic Fibrosis, Extrahepatic Biliary Atresia, Pediatric Aids and Werdnig-Hoffmann Disease

Microdissection-point count morphometric study of the myenteric (Auerbach) plexus or esophagus, small intestine, and colon was done for infants and children with acardia (2), ataxia-telangiectasia (5), cystic fibrosis of the pancreas (CFP) (25), extrahepatic biliary atresia (EBA) (17), pediatric AIDS (10), and Werdnig-Hoffmann disease (WHD) (8). Values for fractional area of neural tissue in the plane of the plexus were compared to those of control patients in same age range as those in each disease category by t-test. Statistically abnormal values included low values for small intestine and colon in Werdnig-Hoffmann disease, high values for small intestine and colon in biliary atresia, and high value for colon but a low value for small intestine in cystic fibrosis. Values for all three loci were within the normal range for ataxia telangiectasia and pediatric AIDS. The mechanisms of the low value for small and large intestines in WHD, which causes chronic constipation as a result of skeletal muscle weakness, and of the high values for colon in CFP and EBA, both causing malabsorption with bulky stools, are unclear. The value for small intestine in acardia was normal for term but lower than expected for fetal bowel of the same size, possibly because of reduced neural crest inflow to the fetal bowel.