Walter E. Berdon

Situs inversus, bronchiectasis, and sinusitis and its relation to immotile cilia: history of the diseases and their discoverers—Manes Kartagener and Bjorn Afzelius

The relationship of Kartagener’s syndrome to immobile cilia syndrome is a fascinating merging of clinical observations and basic science in Zurich, Stockholm, and Toronto. In 1933, Manes Kartagener, a Zurich pulmonary physician, reported four patients with the triad of sinusitis, bronchiectasis, and situs inversus. In the following decades, he reviewed reports of hundreds of cases, but the fact that the male patients with the condition never had offspring eluded his notice. In the 1970s, Bjorn Afzelius, a Ph.D. ultrastructuralist from Stockholm, reported cilia immotility in infertile males, some of the cases occurring in families. Half of the cases had Kartagener’s triad. The observation of Afzelius was soon applied to children by Jennifer Sturgess, a Ph.D. ultrastructuralist, and her medical colleagues in Toronto. With over 500 MEDLINE references since 1966 on Kartagener’s and over 1,000 references on immotile cilia, the causes of the pulmonary infections have become clearer as the patients demonstrate impaired clearance of mucus with resultant sinus and bronchial disease. The cause of the situs inversus remains elusive to this day. It is appropriate to call the condition Kartagener-Afzelius syndrome.

Malignancies in pediatric patients with ataxia telangiectasia

Background. Patients with ataxia telangiectasia (AT), known to have an inherent increased susceptibility to the development of cancer, may present with malignancies that are unusual for the patients age, are often difficult to diagnose clinically and radiographically and respond poorly to conventional therapy. Materials and methods. We reviewed the clinical presentation and imaging studies of 12 AT patients who developed malignancies. Results. Eight of the twelve patients developed non-Hodgkins lymphoma (CNS, thorax, bone), two developed Hodgkins disease, and two were diagnosed with gastrointestinal mucinous adenocarcinoma. Conclusion. The lymphomas were commonly extra nodal, and infiltrative rather than mass-like. The recognition of the tumors was often delayed due to confusion with the known infectious complications in AT patients.

Newborns with diaphragmatic hernia: initial chest radiography does not have a role in predicting clinical outcome

BackgroundThe management of life-threatening congenital diaphragmatic hernia (CDH) has undergone significant change over the last two decades. When CDH was felt to be a surgical emergency treated promptly after birth, survival rates of 50% were typical. Recent changes in medical management of these patients prior to surgery have had a dramatic influence on clinical outcome with survival rates over 80%.ObjectiveThis study was performed to assess under the current 80% survival rates whether there is predictive value in the appearance of the initial chest radiograph and clinical outcome in patients with CDH.Materials and methodsInitial chest radiographs on 56 newborns with CDH were retrospectively reviewed for percent aeration of ipsilateral lung, percent aeration of contralateral lung, percent mediastinal shift, and content of hernia and correlated with clinical outcome.ResultsThere was no significant relationship between radiographic analysis of the percent of ipsilateral lung aeration (P=0.43), contralateral aeration (P=0.52) mediastinal shift (P=0.18), or content of hernia and clinical outcome. All CDH lesions tend to “look the same” on radiographs, regardless of favorable or fatal outcome.ConclusionChest radiography serves to confirm the diagnosis of CDH, but does not predict outcome.

Copper Deficiency Presenting as Metabolic Bone Disease in Extremely Low Birth Weight, Short-Gut Infants

Copper deficiency can cause bone lesions in infants, which might be confused with child abuse. Two extremely low birth weight preterm infants had complicated medical courses requiring prolonged parenteral nutrition for short-gut syndrome, which led to the development of cholestasis. Both had spent their entire lives in the hospital. They had been on prolonged ventilator support for chronic lung disease. They developed signs of copper deficiency between 5 and 6 months of age, initially raising child abuse concerns. Musculoskeletal discomfort led to the recognition of radiographic findings of metabolic bone disease. Included were osteoporosis, metaphyseal changes, and physeal disruptions. Copper levels were low; both low copper parenteral nutrition and gut losses from refeeding diarrhea likely contributed to their deficiency. Therapeutic supplementation with copper corrected their deficits and clinical and radiologic findings. The information from these cases, in particular, their radiologic findings, indicate the need to monitor copper status in at-risk premature infants. These findings may aid prevention and earlier recognition of copper deficiency. Their specific radiologic and clinical findings should aid differentiation of such children from abused infants.

MRI assessment of bronchial compression in absent pulmonary valve syndrome and review of the syndrome.

Absent pulmonary valve syndrome (APVS) is a rare cardiac malformation with massive pulmonary insufficiency that presents with short-term and long-term respiratory problems secondary to severe bronchial compression from enlarged central and hilar pulmonary arteries. Association with chromosome 22.Q11 deletions and DiGeorge syndrome is common. This historical review illustrates the airway disease with emphasis on assessment of the bronchial compression in patients with persistent respiratory difficulties post-valvular repair. Cases that had MRI for cardiac assessment are used to illustrate the pattern of airway disease.

Punctate thymic calcification in infants with untreated Langerhans' cell histiocytosis: Report of four new cases

Abstract Four new cases of punctate thymic calcification in infants with untreated Langerhans cell histiocytosis (LCH) are added to the four previously reported cases. All cases were shown on CT scans; plain films were rarely diagnostic. Pathologic correlation remains elusive since the usual biopsies of the LCH have been on skin or bone biopsies. A single prior pathologic study of the thymus in untreated LCH showed microscopic calcospherites. The thymic punctate calcific densities in patients with LCH may represent further accretion so that the calcospherites become macroscopic. The finding of such punctate calcific densities in an enlarged thymus of an infant with skin or bone or lung disease is strongly suggestive of LCH.

Neuroblastoma arising from the organ of Zuckerkandl: an unusual site with a favorable biologic outcome

Background. Prognosis in neuroblastoma has been shown to correlate with age and stage at diagnosis and site of origin. Extra-abdominal tumors (chest, neck, pelvis) do better in terms of survival than tumors arising from the upper abdomen. Objective. We evaluated a subgroup of abdominal neuroblastomas arising near to the aortic bifurcation (commonly called organ of Zuckerkandl, O. Z.) to assess their biologic outcome and problems in diagnosis and therapy. Materials and methods. Sixteen O. Z. primary tumors were seen at three childrens hospitals. Their clinical records and imaging studies were reviewed, including the sonographic, CT, and MRI findings. When available, MYCN amplification was noted (MYCN is the current term previously called N-MYC). Results. Despite more than half of the tumors being very large, survival was the rule, with only one fatality (following multiple local recurrences). Only one patient (who survived) had bone metastases. The larger masses were usually palpated in otherwise well children, while the smaller ones were found in the course of evaluation for unrelated problems such as urinary tract infection. Intraspinal extension was common, though usually asymptomatic. MYCN amplification was absent in the four patients studied. Conclusions. Lower abdominal (O. Z.) neuroblastomas present technical problems of surgical removal, but form a group with a favorable outcome similar to cervical and thoracic primary sites. MRI was useful in delineating intraspinal extension.

More on Kartagener's syndrome and the contributions of Afzelius and A.K. Siewert

Received: 23 March 2004 Accepted: 29 March 2004 Published online: 26 May 2004 Springer-Verlag 2004 The recent paper on Kartagener, Afzelius and immotile cilia syndrome [1] has evoked unexpected response. The first issue refers to Dr. Afzelius and Dr. Kartagener. Dr. Afzelius offered some additional history. He actually had started his observations in 1959, in sea urchin sperm, where he described dynein arms and offered the hypothesis that the dynein arms make the microtubules slide relative to each other, causing the cilia and flagella to beat. In 1974, he acted as opponent in the dissertation defense of a Danish colleague, Henning Pederson, who showed Dr. Afzelius his unpublished electron micrograph of an immotile human sperm tail lacking dynein arms. Afzelius asked him to publish this finding as soon as possible, which he did. Afzelius returned to Stockholm and contacted the andrologist, Dr. Rune Eliasson, and asked him whether he knew of any men who had stiff, immotile sperm tails; Eliasson knew of two brothers with this type of sperm, who gave ejaculates to be examined by electron microscopy. Pederson and Afzelius published their papers at the same time in 1975, and Afzelius informed Eliasson that one of the brothers and a third unrelated man had immotile spermatozoa and situs inversus and problems with organs having ciliated epithelia. Pederson and Afzelius succeeded in obtaining ciliated epithelia from them and showed the cilia lacked dynein arms; that was in 1976. Pederson died a short time thereafter. Dr. Afzelius is still active in 2004 at the age of 78. Finally,Dr.Afzelius states that his first letter to Dr. Kartagener asking about male sterility was answered by Kartagener, who said that his patients were children. In a follow-up letter Dr. Afzelius told Dr. Kartagener he thought he had an explanation for the triad. Dr. Kartagener’s daughter replied that he had died. Afzelius had intended to inform him about dynein arms; evidently this was never brought to Dr. Kartagener’s attention. The next concerns Dr. A.W. Siewert, who was referenced by Kartagener in 1933 as having published a case in 1904 of situs inversus, dextrocardia and bronchiectasis [2]. Though known to us, this case was not commented on in our paper since the focus of the paper was on the contributions of Kartagener and Afzelius and did not pretend to be an exhaustive review of ‘‘who named it first.’’ Strangely enough, when looking up the triad syndrome, we found that there are over a dozen references to Siewert’s paper on bronchiectasis, situs inversus and dextrocardia, but the syndrome is called Kartagener-Zivat or Zivert or Sivert; all of these papers were from Eastern Europe. Recently, Dr. Chris Pediatr Radiol (2004) 34: 585–586 DOI 10.1007/s00247-004-1203-y LETTER TO THE EDITOR

Gastric thumbprinting: diffuse gastric wall mucosal and submucosal thickening in infants with ductal-dependent cyanotic congenital heart disease maintained on long-term prostaglandin therapy.

Seven infants with ductal dependent cyanotic congenital heart disease are reported. All were on prostaglandin E1 therapy to maintain ductus patency. All showed chest radiographic evidence of multiple masses indenting the stomach lumen (gastric thumbprinting). Other than feeding intolerance in two patients, the findings were incidental and disappeared with cessation of PGE1 therapy. Gastric thumbprinting appears to be a more common consequence of PGE1 therapy than actual obstructing antral masses (antral foveolar hyperplasia).

Ureteral obstruction secondary to indinavir in the pediatric HIV population.

Abstract Indinavir sulfate is a protease inhibitor used in the treatment of the human immunodeficiency virus (HIV). This case report describes the radiographic and urologic manifestations of indinavir urolithiasis in two pediatric patients with acquired immunodeficiency syndrome (AIDS). Management involves aggressive hydration and surgical intervention when indicated.