Infradiaphragmatic totally anomalous pulmonary venous return with two separate descending veins in association with right atrial isomerism.

We present the case of a 1-month-old infant with right atrial isomerism and complex functionally univentricular heart disease, in whom totally anomalous pulmonary venous return drained below the diaphragm via two separate vertical veins. One of the descending vertical veins drained the entire right lung and the left upper lobe, while the other drained the remainder of the left lung. Only one similar case has been described previously.

Metabolic aspects of myocardial disease and a role for L-carnitine in the treatment of childhood cardiomyopathy.

OBJECTIVES: A multicenter retrospective study was conducted to investigate the possible metabolic causes of pediatric cardiomyopathy and evaluate the outcome of patients treated with L-carnitine. METHODS: Seventy-six patients diagnosed with cardiomyopathy were treated with L-carnitine in addition to conventional cardiac treatment, and 145 patients were treated with conventional treatment only. There were 101 males and 120 females between 1 day and 18 years old. Cardiomyopathy diagnoses included dilated (148 patients), hypertrophic (42 patients), restrictive (16 patients), mixed diagnosis (11 patients), and 4 with an unknown type. Of 76 L-carnitine-treated patients, 29 (38%) had evidence to suggest a disorder of metabolism, and of 145 control patients, 15 (10%) were suspected to have a disorder of metabolism. These metabolic disorders were thought to be the cause for the cardiomyopathy of the patients. The duration of L-carnitine treatment ranged from 2 weeks to >1 year. Information was collected on length of survival (time-to-event), clinical outcome, echocardiogram parameters, and clinical assessments. Data were collected at intervals from baseline to study endpoint, death, transplant, or last known follow-up visit. RESULTS: L-Carnitine-treated patients were younger than control patients and had poorer clinical functioning at baseline, yet they demonstrated lower mortality and a level of clinical functioning and clinical severity comparable to control patients on conventional therapy by the end of the study. An analysis of the interaction between clinical outcome and concomitant medications unexpectedly revealed that the population of patients treated with angiotensin-converting enzyme (ACE) inhibitors (40% of patients) had significantly poorer survival (although their greater likelihood for poor survival may possibly have made them more likely to receive ACE inhibitors). CONCLUSION: Results suggest that L-carnitine provides clinical benefit in treating pediatric cardiomyopathy. There is a need for further exploration of potential explanatory factors for the higher mortality observed in the population of patients treated with ACE inhibitors.

Surgical approach to complicated cervical aortic arch: anatomic, developmental, and surgical considerations.

BACKGROUND: Abnormalities of brachiocephalic arterial branching and arch laterality are common in patients with a cervical aortic arch. In addition, structural anomalies of the arch such as obstruction, aneurysms, and tortuosity are found in a significant number of cases. METHODS: Between 1990 and 1998, 6 patients underwent surgery for an obstructed right cervical arch. A significant obstruction was present at the transverse or distal arch in all patients, and was recurrent after previous repair in 2. In 1 patient, there was also a multi-lobed aneurysm of the aortic segment contiguous to the obstruction, and in 2 there was marked tortuosity of the arch. In all cases, the order of origin of the head and neck vessels was abnormal, and obstruction of 1 or more brachiocephalic vessels was found in 3. A vascular ring was present in all patients, with a right aortic arch and aberrant left subclavian artery in 4 patients and a double aortic arch with a dominant right cervical arch in 2. The descending aorta was circumflex (left-sided) in 3 patients. Three patients were repaired through a standard right posterolateral thoracotomy, and 3 through a median sternotomy. Patch augmentation aortoplasty was used in 2 patients, a tube graft from the ascending to descending aorta in 2, end to side anastomosis of the descending aorta to the proximal arch in 1, and direct anastomosis to reconstruct an atretic left-sided component of a double arch in 1. RESULTS: Repair was successful in all cases, with no perioperative complications. At follow-up ranging from 1 to 9 years, all patients were alive and well, with no recurrence of arch obstruction or other significant complications. Fluorescent in situ hybridization revealed microdeletion of chromosome 22q11 in 1 patient (not performed in the others). CONCLUSIONS: Structural anomalies of the arch are relatively common in patients with a cervical aortic arch. Such abnormalities may be the result of hemodynamic conditions and/or abnormal vascular tissue related either to the cervical position of the arch or its embryologic precursors. Given the highly variable anatomy of patients with a complicated cervical aortic arch, surgical considerations will vary in kind.

Gastroesophageal reflux after repair of atrioventricular septal defect in infants with trisomy 21: a comparison of medical and surgical therapy.

BACKGROUND: Gastroesophageal reflux and dysmotility are common in children with trisomy 21. Children with trisomy 21 and congenital heart disease are at increased risk for complications of gastroesophageal reflux even after repair of their cardiac abnormalities. The optimal management of reflux in these patients is not known. METHODS: The authors studied 24 consecutive infants (5.3+/-3.1 months) with trisomy 21 and atrioventricular septal defect who had symptoms or signs of gastroesophageal reflux and a positive esophageal pH study finding early after repair of their cardiac anomaly. Ten patients were given standardized medical therapy with upright positioning during and after feedings, thickening of feedings, metoclopramide, and an H2-receptor antagonist. The other 14 underwent primary surgical management consisting of Nissen fundoplication through a minilaparotomy. RESULTS: All 10 medically treated patients required readmission within 2 weeks for complications related to reflux, including aspiration or pneumonia (n = 6), persistent failure to thrive (n = 2), and frequent apneic episodes (n = 2). No surgically treated patients had reflux-related complications requiring readmission. The total duration of hospitalization in the medically treated patients, including the initial hospitalization and the rehospitalization, was significantly longer than in patients who underwent fundoplication (35.8+/-9.8 v. 10.4+/-2.2 days, P<.001). At follow-up (24 to 56 months), all patients were alive except for 1 medically treated patient who died of aspiration pneumonia 28 days after readmission. Two medically treated patients required a Nissen, and 3 patients in the surgical group underwent redo fundoplication, all within 1 year. Three other patients in the medically treated group required a total of 8 hospitalizations for complications of reflux. No patient in either group required placement of a gastrostomy tube. Weight percentile for age was higher in surgical than medical patients. CONCLUSIONS: Infants with trisomy 21 and atrioventricular septal defect who undergo fundoplication are less likely to experience major complications of reflux early after cardiac surgery than those treated with a medical regimen of upright posture, thickened feedings, metoclopramide, and H2-receptor blockade.

Marked left ventricular hypertrophy in children on tacrolimus (FK506) after orthotopic liver transplantation.

Although the cardiac effects of tacrolimus (FK506) have not been well documented, clinical cases of children on FK506 who developed hypertrophic obstructive cardiomyopathy have been reported. We report 2 cases of marked concentric hypertrophy of the left ventricular myocardium found at autospy in children on FK506.

The role of L-carnitine in pediatric cardiomyopathy.

Metabolic and genetic factors underlie some forms of cardiomyopathy in childhood. A variety of inborn errors of metabolism can impair mitochondrial energy production, or beta-oxidation, in the heart and lead to myocardial dysfunction. L-Carnitine, an essential element of beta-oxidation, transports fatty acids across the mitochondrial membrane for energy production. L-Carnitine deficiency syndromes are now well described as secondary to a variety of inborn errors of metabolism and often include cardiomyopathy in the clinical picture. Despite traditional therapies for cardiomyopathy, mortality for this disorder remains at well over 50%. Review of reports of L-Carnitine supplementation studies and results from our own trial underscore the importance of its role in cardiac function and demonstrates that there is likely a subpopulation of patients with cardiomyopathy responsive to L-carnitine treatment.

Regulated synthesis and localization of DNA methyltransferase during spermatogenesis.

Differences in the methylation patterns of male and female gamete DNA are likely to be involved in genomic imprinting. However, little is known of the mechanisms that regulate de novo methylation and demethylation during gametogenesis. We report here that the well-characterized M(r) 190,000 form of DNA methyltransferase (the only known form) is present in isolated mitotic, meiotic, and postmeiotic male germ cells, with the exception of meiotic pachytene spermatocytes, where the protein is undetectable by immunoblot analysis and a novel 6.2-kb DNA methyltransferase transcript is present. Whereas replication and methylation are coupled in somatic cells, the presence of DNA methyltransferase in postreplicative male germ cells is consistent with previously observed de novo methylation events in these cells. Immunofluorescence experiments revealed that DNA methyltransferase is localized to the nuclei of male germ cells, with a subset of spermatogonia and postreplicative leptotene/zygotene spermatocytes displaying prominent nuclear foci that are strongly enriched in DNA methyltransferase. The data suggest that down-regulation of DNA methyltransferase expression during the pachytene stage of meiosis utilizes an mechanism that is associated with the production of a larger mRNA, and that de novo methylation in leptotene/zygotene spermatocytes may take place in spatially restricted nuclear domains that are enriched in DNA methyltransferase.

Developmental and hormonal regulation of DNA methyltransferase in the rat testis.

Changes in DNA methylation patterns during gametogenesis have been implicated in the regulation of germ cell development and genomic imprinting. Cytosine methylation is catalyzed by the enzyme DNA (cytosine-5)-methyltransferase (DNA MTase). The objective of this study was to determine the presence and study the developmental and hormonal regulation of DNA MTase expression in the rat testis. Northern blots of RNA isolated from 10 different adult rat tissues were used to determine tissue-specific differences in transcript size and abundance of DNA MTase. The developmental regulation of DNA MTase in the rat testis was examined by use of Northern blots of testicular and isolated germ cell RNA from rats ranging in age from 7 to 91 days. For a better understanding of the hormonal regulation of DNA MTase in the rat testis, adult rats were hypophysectomized and 4 wk later (Day 0) received 24-cm testosterone silastic implants; controls were sham hypophysectomized. At Days 0, 3, 7, 14, 28, and 56, one testis from each rat (n = 4/group) was used to prepare total RNA. Examination of DNA MTase mRNA expression in different rat tissues demonstrated the existence of a single 5.2-kb transcript; up to 5-fold tissue-specific variations in the levels of DNA MTase mRNA between the tissue with the highest expression, spleen, and that with the lowest expression, prostate; and significant levels of expression in the testis (three times prostate levels). During testicular development, DNA MTase mRNA levels were highest at 7-21 days of age and decreased by 45% by Day 28; mRNA levels decreased further to reach steady adult levels by Day 42.(ABSTRACT TRUNCATED AT 250 WORDS)

Aortic subannular ventricular aneurysms.

Subannular aneurysms of the left ventricle are rare aneurysms originating adjacent to the aortic or mitral valve. Mitral subannular aneurysms are more common and have been well described. Two cases of aortic subannular aneurysm are reported, and an additional 20 cases were found in the literature. These aneurysms are usually found in young adults who may be seen with congestive heart failure, cardiac murmurs, angina pectoris, myocardial infarction, or even rupture. The aneurysms are often associated with aortic valve anomalies or subaortic stenosis. Diagnosis can be made by echocardiography and cardiac catheterization, and surgical repair is indicated.

Isolation of chicken phosphotyrosyl phosphatase cDNA sequences and identification of a brain-specific species related to human PTP zeta.

The first example of a chicken cDNA sequence encoding a phosphotyrosyl phosphatase (PTPase) has been identified and found to contain coding sequences for the entire cytoplasmic and membrane spanning domains as well as a portion of the extracellular region of a transmembrane PTPase resembling human PTP zeta. Like HPTP zeta, chicken PTP zeta contained two phosphatase domains (D1 and D2), and D2 lacked a critical cysteine residue required for catalytic activity. The entire intracellular portion of CPTP zeta was expressed in bacteria and shown to be capable of dephosphorylating both p-nitrophenylphosphate and reduced carboxyamidomethylated and maleyated lysozyme but not phosphoseryl casein. Genetic analysis indicated that the presence of D2 was required for full activity. CPTP zeta mRNA was identified as a single large transcript expressed exclusively in the brain of chick embryos at both early and late stages of embryogenesis. These results suggested that CPTP zeta may perform a brain-specific function and have a role in development.

Isolated noncompaction of left ventricular myocardium. A study of eight cases.

Isolated noncompaction of left ventricular myocardium is a rare disorder of endomyocardial morphogenesis characterized by numerous, excessively prominent ventricular trabeculations and deep intertrabecular recesses. This study comprised eight cases, including three at necropsy. Ages ranged from 11 months to 22.5 years, with follow-up as long as 5 years. Gross morphological severity ranged from moderately abnormal ventricular trabeculations to profoundly abnormal, loosely compacted trabeculations. Echocardiographic images were diagnostic and corresponded to the morphological appearances at necropsy. The depths of the intertrabecular recesses were assessed by a quantitative echocardiographic X-to-Y ratio and were significantly greater than in normal control subjects (p less than 0.001). Clinical manifestations of the disorder included depressed left ventricular systolic function in five patients, ventricular arrhythmias in five, systemic embolization in three, distinctive facial dysmorphism in three, and familial recurrence in four patients. We conclude that isolated noncompaction of left ventricular myocardium is a rare if not unique disorder with characteristic morphological features that can be identified by two-dimensional echocardiography. The incidence of cardiovascular complications is high. The disorder may be associated with facial dysmorphism and familial recurrence.

[Restriction map of E. coli shuttle plasmid (p# GTE5) with secretive function].

The shuttle plasmid (p# GTE5) DNA with secretive function was extracted by the alkali lysozyme method from E. coli RRI strain. Its molecular weight is 4.5 Md and DNA size is 6.9 Kb. Restriction fragments of plasmid was obtained by single and double enzymes complete digestion using five different restriction endonucleases. The restriction map of shuttle plasmid (p# GTE5) was established for the enzymes EcoRI, BglII, pstI, PvuII, and TaqI.

Pulmonary vascular sling: report of seven cases and review of the literature.

A total of 130 cases of pulmonary vascular sling, including seven new cases in our collection, were studied. The sex distribution was 60% male and 40% female. The age at presentation was in the first year of life in approximately 90% of cases. Barium-esophagraphy showing anterior indentation was diagnostic in most of the cases. Bronchoscopy and tracheobronchography were useful in detecting associated tracheobronchial anomalies preoperatively. The analysis of 68 autopsied cases revealed associated tracheobronchial anomalies in 40% of the cases. Anomalies of the tracheobronchial tree took three major forms: abnormal distribution of cartilage in the walls of the trachea and major bronchi, intrinsic stenosis, and abnormal branching, the latter being that of bronchus suis. Acquired changes secondary in the sling resulted in compression of the major respiratory pathway by the anomalous left pulmonary artery. Major associated cardiovascular anomalies were present in 30% of the cases. These were represented by ventricular septal defect, atrial septal defect, patent ductus arteriosus, tetralogy of Fallot, common ventricle, and coarctation of the aorta.

Prenatal closure of the foramen ovale in complete transposition of great vessels. Observations in a case with intact ventricular septum and normally developed left heart chambers.

A rare case is reported of premature closure of the foramen ovale in d-transposition of the great vessels with intact ventricular septum and normal development of the left side of the heart. Asphyxia neoatorum and cardiac failure were the manifestations in the early neonatal period. Balloon atrial septostomy during cardiac catheterization would be unsuccessful in infants with this condition, and closed atrial septectomy (Blalock-Hanlon procedure) would be necessary for survival.