Delayed contrast enhancement magnetic resonance imaging in congenital aortic stenosis.

We report a case of a 12-year-old boy with severe congenital aortic stenosis in whom magnetic resonance imaging (MRI) with delayed contrast enhancement demonstrated extensive subendocardial hyperenhancement within the left ventricle. The hyperenhancement was confirmed to be subendocardial infarct and fibrosis by histopathology. This case supports the utility of MRI with delayed contrast enhancement in evaluating myocardial viability in patients with congenital heart disease.

Components in seminal plasma regulating sperm transport and elimination.

Seminal plasma has been suggested to be involved in sperm transport, and as a modulator of sperm-induced inflammation, which is thought to be an important part of sperm elimination from the female reproductive tract. This article reports on recent experiments on the importance of seminal plasma components in sperm transport and elimination. In Experiment 1, hysteroscopic insemination in the presence (n = 3) or absence (n = 3) of 2 ng/mL PGE showed an increased portion of spermatozoa crossing the utero-tubal junction in the presence of PGE in two mares, while no difference was observed between treatments in a third mare. In Experiment 2, whole seminal plasma, heat-treated seminal plasma (90 degrees C for 45 min), and charcoal-treated seminal plasma were added to: (1) sperm samples during opsonization prior to polymorphonuclear neutrophil(s) (PMN)-phagocytosis assays (n = 5); or to (2) phagocytosis assays (n = 5). Opsonization of spermatozoa was suppressed in the presence of whole seminal plasma, compared with samples without seminal plasma (p < 0.05). Charcoal treatment did not remove the suppressive effect of seminal plasma on opsonization, but heat treatment of seminal plasma reduced its suppressive properties (p < 0.05). The addition of whole seminal plasma to opsonized spermatozoa almost completely blocked phagocytosis (p < 0.05). Charcoal treatment did not remove the suppressive effect of seminal plasma. However, heat-treated fractions of seminal plasma removed the suppressive effect of seminal plasma on phagocytosis (p < 0.05). In Experiment 3, viable and non-viable (snap-frozen/thawed) spermatozoa were subjected to in vitro assays for PMN binding and phagocytosis with the following treatments (n = 3): (1) seminal plasma (SP), (2) extender; (3) ammonium sulfate precipitated seminal plasma proteins with protease inhibitor (SPP+); or (4) ammonium sulfate precipitated seminal plasma proteins without protease inhibitor (SPP-). Treatment was observed to impact binding and phagocytosis of viable and non-viable spermatozoa (p < 0.05). SP and SPP+ suppressed PMN-binding and phagocytosis of viable sperm. This effect was also seen, but to a lesser degree, in SPP- treated samples. Non-viable spermatozoa showed less PMN-binding and phagocytosis than live sperm in the absence of SP. The addition of SP promoted PMN-binding and phagocytosis of non-viable spermatozoa. SPP- treated samples also restored PMN-binding of non-viable spermatozoa. The addition of protease inhibitors removed this effect. In Experiment 4, seminal plasma proteins were fractionated based on MW by Sephacryl S200 HR columns (range 5000-250,000 kDa). Fractionated proteins were submitted to sperm-PMN binding assays. A protein fraction <35 kDa suppressed PMN-binding to live and snap-frozen spermatozoa. A greater MW protein fraction appeared to promote binding between PMNs and snap-frozen spermatozoa. While the addition of protease inhibitors was necessary to maintain the protective effect of seminal plasma proteins on viable spermatozoa, the promotive effect of seminal plasma on non-viable spermatozoa appeared to require some protease activity. It was concluded from these experiments that components of seminal plasma play active roles in transportation and survival of viable spermatozoa in the female reproductive tract and in the elimination of non-viable spermatozoa from the uterus.

Interaction between equine semen and the endometrium: the inflammatory response to semen.

Insemination of mares with bacteria-free equine spermatozoa results in an influx of polymorphonuclear neutrophils (PMNs) into the uterine lumen. In vitro studies have demonstrated that equine spermatozoa activate complement, resulting in cleavage of factors C5a and C3b. Since uterine secretion is rich in complement, it is likely that an interaction between spermatozoa and uterine secretion results in C5a-mediated chemotaxis and migration of PMNs into the uterine lumen. Once in the uterine lumen, the PMNs phagocytize bacteria and spermatozoa, which is an important part of sperm elimination from the reproductive tract. It is not clear how the spermatozoa are opsonized, or if phagocytosis of equine spermatozoa is a selective or non-selective process. Breeding-induced endometritis appears to be both up and down regulated by seminal components. A modulatory role on the inflammation has been suggested for equine seminal plasma. Seminal plasma suppressed complement activation, PMN-chemotaxis and phagocytosis in vitro. Preliminary in vivo experiments also support a suppressive role of seminal plasma in breeding-induced endometritis. The duration but not the magnitude of the PMN-influx into the uterine lumen was shortened when seminal plasma was included in an insemination dose. The presence of PMNs in the uterus affects the motion characteristics of spermatozoa in vitro. Both progressive motility and mean path velocity were impaired when spermatozoa were incubated in uterine secretion from mares with ongoing breeding-induced endometritis. The binding of spermatozoa to PMNs was prominent in all samples collected from mares with an ongoing endometritis. The motility remained impaired, but the binding of the spermatozoa to PMNs was reduced when the spermatozoa were incubated in uterine secretion in the presence of seminal plasma. Preliminary characterization of the immune-suppressive component in seminal plasma suggests that it is one or more molecule(s) with a molecular weight between 50 and 100 kDa, partially inactivated by charcoal stripping and partially heat-inactivated at 95 degrees C for 45 min.

Pulmonary atresia with intact ventricular septum, right-sided aortic arch and ventriculocoronary connection--prenatal echocardiographic diagnosis.

The authors describe the prenatal echocardiographic diagnosis of a rare case of pulmonary atresia with intact ventricular septum, right-sided aortic arch, and ventriculocoronary connection in a fetus at 21 weeks gestation. The diagnosis was confirmed at autopsy.

Severe pulmonary hypertensive vascular disease in two newborns with aneurysmal vein of galen.

Arteriovenous malformation of the vein of Galen (AVG) is a rare entity in the newborn with a high morbidity and mortality. We present two cases of fatal AVG with persistent pulmonary hypertension of the newborn and significant pulmonary hypertension documented by autopsy histopathology. The pathophysiology is reviewed and a proposed mechanism of the association between AVG and pulmonary hypertension is discussed.

Intrinsic hyperreactivity of mucosal T cells to interleukin-2 in pediatric Crohn's disease.

OBJECTIVES: To cells play a crucial role in many chronic inflammatory diseases. Mucosal T cells are particularly important in the pathogenesis of Crohn's disease (CD). We investigated the response of T cells in CD and other intestinal inflammatory conditions to interleukin-2 (IL-2), a cytokine essential for T-cell activation, growth, and function. STUDY DESIGN: T-cell reactivity was assessed by measuring growth induced by IL-2 in mucosal endoscopic biopsy specimens obtained from children with CD, ulcerative colitis, indeterminate colitis, and chronic nonspecific colitis and from children without gastrointestinal inflammation. RESULTS: CD mucosal T cells grew remarkably and significantly more than T cells from normal, ulcerative colitis, and chronic nonspecific colitis mucosa. T cells from indeterminate colitis mucosa grew similarly to those of CD mucosa. The enhanced growth response in CD was independent of disease location, presence or absence of intestinal inflammation, treatment, disease duration, or clinical activity. CONCLUSION: Mucosal T cells from children with CD exhibit an intrinsic hyperreactivity to IL-2. This may represent a primary pathogenic abnormality in this condition.

Genetic and morphological findings in progressive familial intrahepatic cholestasis (Byler disease [PFIC-1] and Byler syndrome): evidence for heterogeneity.

Byler disease (ByD) is an autosomal recessive disorder in which cholestasis of onset in infancy leads to hepatic fibrosis and death. Children who have a clinically similar disorder, but are not members of the Amish kindred in which ByD was described, are said to have Byler syndrome (ByS). Controversy exists as to whether ByD and ByS (subtypes of progressive familial intrahepatic cholestasis [PFIC]) represent one clinicopathological entity. The gene for ByD has been mapped to a 19-cM region of 18q21-q22. PFIC caused by a lesion in this region, including ByD, can be designated PFIC-1. Examination of haplotypes in siblings with ByS in two unrelated non-Amish families showed that the gene(s) responsible for their disorder(s) did not lie in the PFIC-1 candidate region. On light microscopy and transmission electron microscopy (TEM), liver tissue differed between Amish children with PFIC-1, who had coarsely granular bile and at presentation had bland intracanalicular cholestasis, and the children with ByS in the two non-Amish families, who had amorphous or finely filamentous bile and at presentation had neonatal hepatitis. Bile acid composition of bile also differed: In the Amish children with PFIC-1 and in one ByS family, the proportional concentration of chenodeoxycholic acid (CDCA) in bile was low compared with normal bile; in the other ByS family, it was only slightly reduced. Genetic analysis and light microscopy and TEM of liver may help distinguish PFIC-1 from other forms of ByS.

Pulmonary intralobar sequestration in a patient with cystic fibrosis.

We report a case in which pulmonary Intralobar Sequestration (ILS) was an incidental finding at autopsy in an adult with Cystic Fibrosis. Two aberrant arteries from the descending thoracic aorta supplied a bronchial cystic lesion in the right lower lobe. Termination of the segmental bronchus and scar formation proximal to the cyst suggested prior bronchial obliteration. The elastic configuration of the aberrant aortic-derived vessels of the sequestration contrasted sharply with massively hypertrophied, muscular, bronchial arteries which supplied the bronchiectatic upper lobe. Sections of inferior pulmonary ligament were studied in five additional patients with CF but without ILS. Small muscular arteries were consistently noted within the inferior pulmonary ligament. These histologic findings support the concept that the vascular portion of ILS is congenital, whereas the bronchocystic component, in some cases, may be acquired.

Liver biopsy findings in patients with juvenile rheumatoid arthritis receiving long-term, weekly methotrexate therapy.

We performed percutaneous liver biopsy in nine children who had received a weekly dose of methotrexate, 10 mg/m2 per week, for at least 3 years to address the concern about subclinical liver toxicity from single, weekly, low-dose methotrexate therapy for juvenile rheumatoid arthritis. No patient had clinical or biochemical evidence of liver injury. All biopsy results were interpreted as normal. These results suggest that the recommendations of the American College of Rheumatology for adults receiving single weekly methotrexate therapy for rheumatoid arthritis can be extended to children.

Renal histological changes secondary to ureteropelvic junction obstruction.

The treatment of children with apparent ureteropelvic junction obstruction is controversial. In an asymptomatic infant or child the decision to recommend pyeloplasty usually is based on interpretation of the renal scan. We retrospectively analyzed the renal biopsy obtained during pyeloplasty in 55 children. Histological changes were compared to the differential renal function revealed on the preoperative renal scan. Histological changes were graded on a scale of I to V; I--normal, II--mild dilatation of the collecting tubules or Bowman's space and III to V--progressively severe changes of obstructive uropathy, including reduced glomerular number, glomerular hyalinization, cortical cysts and interstitial inflammation. Patient age ranged from 4 days to 19 years (mean 4.8 years). Mean differential function according to histological grade was I--49%, II--43%, III--42%, IV--30% and V--25%. Of 33 patients with a differential function of 40% or greater 26 (79%) had a grade I or II biopsy, while 21% had a more significant alteration in renal histology. In contrast when the differential function was less than 40% 6 of 18 patients (33%) had grade I or II disease on biopsy. In conclusion, in approximately 25% of children with ureteropelvic junction obstruction there is a disparity between preoperative differential renal function computed during diuretic renography and renal biopsy.

Cutaneous bronchogenic cyst of the back: a case report and review of the literature.

Cutaneous and subcutaneous cysts with ciliated pseudostratified columnar (respiratory) epithelium present a diagnostic dilemma. We report a case of a bronchogenic cyst occurring on the back. The differential diagnosis includes branchial cleft cyst, thyroglossal duct cyst, cutaneous ciliated cyst, and mature cystic teratoma. We review reports of extrapulmonary bronchogenic cysts and discuss their possible embryology.

Influence of vas deferens mobilization on rat fertility: implications regarding orchiopexy.

Children who undergo bilateral orchiopexy often have oligospermia or azoospermia in adulthood. This subfertility generally has been attributed to histological alterations in the cryptorchid testis. However, the possibility that an iatrogenic factor, such as mobilization of the vas deferens during orchiopexy, may have an adverse effect on fertility has not been studied. Six groups of mature Sprague-Dawley rats underwent right orchiectomy and the following procedures on the left side: group 1--sham operation, group 2--2 cm. of vas mobilized, group 3--4 cm. of vas mobilized, group 4--2 cm. of vas mobilized and deferential artery stripped off of vas, group 5--4 cm. of vas mobilized and deferential artery stripped off of vas and group 6--vasectomy. Each rat was then housed with 2 female rats for 24 days. Mobilization of the vas with disruption of the mesentery resulted in slight but statistically insignificant reduction in fertility. However, when the deferential artery was dissected off the vas, there was a marked reduction in fertility and fecundity. Histologically the vasa were normal without evidence of ischemic necrosis. The testes in groups 2 to 5 showed variable depletion of germ cells with shedding of germinal epithelium, and the testes and epididymides in group 5 were similar to the changes seen in vasectomized rats (group 6). No testes were necrotic. These data suggest that extensive mobilization of the vas causes subfertility in this animal model and may be secondary to a functional obstruction resulting from vas denervation. Whether a similar effect occurs during orchiopexy in humans deserves study.

Morphometric analysis of the lung in bronchopulmonary dysplasia.

We studied lung development in children with or without bronchopulmonary dysplasia (BPD) using light microscopic morphometry and thick lung sections stained for elastic fibers. One lung was obtained at autopsy from each of eight patients with BPD (ages, 2 to 28 months) and six children (ages, 5 days to 51 months) who died without lung disease. Patients with BPD demonstrated severe somatic growth retardation and had reduced lung volumes with abnormal lobar volume proportions. In the central bronchi mean volume proportion of glands and smooth muscle was increased in BPD. Bronchiolar density was also increased, but it tended to normalize with advancing age. Mean bronchiolar diameter was slightly smaller in BPD, and bronchiolar smooth muscle hypertrophy was a constant histologic feature. The most striking change, however, was noted in alveolar structure and development. Total alveolar number was severely decreased in patients with BPD compared with that in control subjects, and there was little evidence of compensatory alveolar development with increasing age. Lung internal surface area was correspondingly reduced, and mean linear intercept was increased. Sections stained for elastic tissue demonstrated in the patients with BPD a simplified acinar structure with thickened, tortuous, and irregularly distributed alveolar elastic fibers. We conclude that in severe, fatal BPD there is marked impairment of lung development with alveolar hypoplasia and reduced internal surface area. In addition, bronchial and bronchiolar smooth muscle hypertrophy and bronchial gland hyperplasia may be important contributing factors to airflow limitation.

Pathology of neonatal necrotizing enterocolitis: a ten-year experience.

We reviewed pathology specimens from 84 patients seen during a 10-year period with neonatal necrotizing enterocolitis, and these findings were correlated with clinical features. Coagulation (ischemic) necrosis, inflammation, and bacterial overgrowth were all present in the intestine of nearly all patients but with individual variability in the severity of these findings. Overall, coagulation necrosis was more severe than any other finding in most infants, indicating the importance of ischemia in the pathophysiology of necrotizing enterocolitis. Reparative tissue changes such as epithelial regeneration, granulation tissue formation, and fibrosis, found in two thirds of cases, suggested ongoing tissue injury of at least several days' duration. Birth weight, Apgar score, age, feeding status, and the presence of respiratory distress syndrome were not correlated with any particular histologic feature. The pathologic changes of necrotizing enterocolitis suggest that its cause is multifactorial, with ischemia, inflammation, bacterial overgrowth, and reparative tissue changes all playing important roles.