Nephromegaly in infancy and early childhood: a risk factor for Wilms tumor in Beckwith-Wiedemann syndrome.

OBJECTIVE: Beckwith-Wiedemann Syndrome (BWS) is an overgrowth syndrome associated with macrosomia, omphalocele, macroglossia, visceromegaly and Wilms tumor (WT). We conducted a case-control study in children with BWS to examine whether nephromegaly increases the risk of WT. METHODS: The BWS Registry was used to identify control and case patients. Control patients were defined as children with BWS who were older than 6 years and had no imaging evidence of renal disease or previous WT and for whom complete records were available; 31 patients met these criteria. Case patients were defined as children with BWS who had WT and screening renal imaging before the diagnosis of WT; 12 of these patients had serial screening images before diagnosis of WT and comprised the study population. Only renal images obtained before the diagnosis of WT was made were used to assess renal length. RESULTS: All 12 patients with WT had nephromegaly (> or =95th percentile of age adjusted renal length) on serial screening studies. Only four of 31 control patients (specificity = 86%) had nephromegaly resulting in an odds ratio of 72 (95% confidence interval = 13-391) for the risk of WT with nephromegaly. CONCLUSIONS: In patients with BWS, persistent nephromegaly is a strong risk factor for the development of WT. If screening for WT is done in this population, infants with nephromegaly should be considered those at greatest risk for WT, and screening may be best targeted at this group.

Pharmacologic manipulation of postoperative labial wound contraction and midfacial growth in rabbits.

Recent experimental work has suggested that increased lip pressure and scar contraction following lip repair with wide soft-tissue undermining may, in part, contribute to midfacial growth inhibition. The present study was designed to test this hypothesis through the application of pharmacologic agents reported to minimize scar contraction. Thirty-six 6-week-old rabbits were divided into six groups: unoperated controls, rabbits with surgically created defects left unrepaired (surgical controls), and four groups of rabbits with surgically created defects with lip repair and wide undermining on the maxillary surface. Animals with lip repair received either no injections or labial subcutaneous injections of distilled water (route-of-injection controls), normal saline, or papaverine hydrochloride for 2 weeks postoperatively. Rabbits with lip repair and saline or papaverine injections showed significantly (p less than 0.05) decreased lip pressure, relatively hypotonic orbicularis oris muscle EMG activity on the cleft lip side, and greater anteroposterior facial growth (assessed radiologically) from 2 to 24 weeks postoperatively compared with rabbits with lip repair and postoperatively compared with rabbits with lip repair and no injections or distilled water injections. Preliminary results suggest that wound contraction following lip repair and soft-tissue undermining may contribute to mid-facial growth inhibition, which may be reduced by pharmacologic manipulations in the rabbit model.

A test of two midfacial growth models using path analysis of normal human fetal material.

Predictions about the temporal sequencing (i.e., primacy) and causal relationships between various midfacial growth components, as suggested by two midfacial growth models (functional matrix and septal traction), were examined in the present study. The relationships between quantitative changes in the nasal septum, nasal airway, nasolabial musculature, and premaxilla of 15 normal human fetal specimens, ranging in age from 12 to 20 weeks postmenstrual age, were assessed using the multivariate technique of path analysis. Path analysis results revealed that the causal sequence of variables proposed by the septal-traction model explained more of the variance in premaxillary size (87 percent goodness-of-fit) than did the sequence of variables proposed by the functional matrix model (65 percent goodness-of-fit). These results suggest that the septal-traction model may be a more parsimonious and primary explanation of early human fetal midfacial growth than the functional matrix model. Path analysis results also reiterate the observed complex developmental relationships within the fetal labioseptopremaxillary region, knowledge of which may be important in the surgical management of infants with complete cleft.

Proteasas (queratinasas) extracelulares en cepas fúngicas queratinofílicas aisladas de suelos chilenos: estudio preliminar / Extracellular proteases (queratinases) in keratinophilic fungi isolated from chilean soils: preliminary study

Se determina la presencia de proteasas extracelulares (queratinasas). "in vitro" en cepas de hongos queratinolíticos y queratinofílicos aislados de suelos chilenos. Se cultivaron durante 15 a 30 días siete cepas de hongos queratinofílicos, tanto en agitación como en forma estática y seis cepas de hongos queratinolíticos sólo en forma estática, en medio líquido que contiene pelo humano tratado como sustrato queratinoso. Las proteasas extracelulares fueron aisladas y purificadas por cromatografía en columna sobre Sephadex G-75. Mediante la electroforesis en gel de poliacrilamida se detectan bandas de proteínas de peso molecular entre 38.000 y 40.000 para Scopulariopsis brumptii, Ulocladium atrum, Botryotrichum piluliferum, Auxarthron umbrinum y Gymnoascus reessii, comparables con la obtenida para Trichophyton mentagrophytes, hongo utilizado como control, lo cual lleva a postular que las enzimas corresponden a queratinasas

Development of the orbicularis oris muscle in normal and cleft lip and palate human fetuses using three-dimensional computer reconstruction.

As part of an ongoing study of cleft lip and palate fetal morphology, normal and dysmorphic development of the human fetal orbicularis oris muscle was studied in a cross-sectional sample of 29 human fetuses (20 "normal" and 9 cleft lip and palate) ranging in age from 8 to 21 postmenstrual weeks. The specimens were embedded in celloidin and sectioned at 20 microns, and every tenth section was stained with hematoxylin and eosin. A computer reconstruction technique was applied to produce three-dimensional representations of the orbicularis oris muscle. The orbicularis oris muscle in the normal fetal sample with discernible lip fibers (N = 15) increased symmetrically in both fiber density and complexity from 12 to 21 weeks. Metrically, muscle volume and thickness growth curves were consistent with qualitative observations. In contrast, the unilateral cleft lip and palate fetal specimens with discernible lip fibers (N = 3) exhibited a 3.5-week delay in overall muscle development, asymmetrical fiber distribution, and abnormal fiber insertions. However, quantitatively, no significant (p greater than 0.05) differences were noted in orbicularis oris muscle thickness or volume between the normal and cleft lip and palate fetal specimens through 21 weeks. Findings suggest that orbicularis muscle deficiency, noted clinically in cleft lip and palate neonates, may be a result of perinatal functional dysmorphogenesis rather than congenital mesenchymal reduction or deficiency.

Analysis of the size variability of the human normal and cleft palate fetal nasal capsule by means of three-dimensional computer reconstruction of histologic preparations.

As part of an ongoing study of cleft palate fetal morphology, normal and dysmorphic development of the human fetal nasal capsule was studied in a cross-sectional sample of 29 human fetuses (20 "normal" and 9 cleft), ranging in age from 8 to 21 postmenstrual weeks. The specimens were celloidin embedded, sectioned at 20 microns, and every tenth section stained with hematoxylin and eosin. A computer reconstruction technique was applied to produce three-dimensional representations of the nasal capsule, nasal septal cartilage, and nasal airway. Qualitatively, the cleft palate nasal capsule exhibited gross abnormalities including cartilaginous nasal septum deformities, abnormal septal volume and hypertrophy, reduced nasal airway and capsule volumes, and abnormal spatial relationships between the nasal capsule components. These results suggest that the reduced nasal airways, noted clinically in cleft perinates, may be a function of an interaction of nasal capsule deficiency and nasal septum hypertrophy. However, when lengths and volumes were plotted against fetal postmenstrual age, producing fetal "growth" curves, no significant differences (p greater than 0.05) were noted for growth rates (slopes) or nasal capsule size between the normal and cleft palate fetal samples. Curvilinear regression analysis revealed that both normal and cleft palate nasal capsule and septum lengths changed in a sigmoidal fashion, with the steepest increases from 13 to 17 weeks. In contrast, nasal capsule, airway, and septum volumes changed curvilinearly, showing slow relative growth rates from 8 to 17 weeks, which increased sharply from 18 to 21 weeks. Results suggest that from 8 to 21 weeks prenatally, normal and cleft palate specimens exhibited a similar pattern of fetal nasal capsule development that was characterized by an initial anteroposterior elongation followed by circumferential (i.e., volumetric) growth.

Congenital pernicious anemia: report of seven patients, with studies of the extended family.

Seven children ages 1 1/2 to 12 years with congenital pernicious anemia were detected in an extended Mexican family. All affected children had megaloblastic anemia accompanied by low serum B12 and normal serum folate levels. Gastric fluid analysis in six patients revealed normal gastric acidity and absent intrinsic factor. Serum antibodies to intrinsic factor or parietal cells were also absent. Schilling tests performed in six of the seven patients yielded abnormal results. Of the three patients in whom gastric biopsy was done, two had normal histologic findings (including examination by electron microscopy) and one had mild atrophy. All patients responded rapidly to parenterally administered vitamin B12 therapy. In addition, 170 family members were screened for the defect with complete blood counts and serum B12 levels. Such screening detected pernicious anemia in two of the children, but no other abnormalities that could be attributed to pernicious anemia were found in other family members. Based on the family pedigree, autosomal recessive inheritance is likely. The variability of age of presentation in this family is noteworthy and suggests that expression may be modified by still undefined factors.

Effect of caloric density on gastric emptying in premature infants.

The role of caloric density in the regulation of gastric emptying has been well documented in adults but studied to only a limited extent in young infants. Ten premature infants were each fed 22 ml/kg formula (Similac Special Care), at concentrations of 24, 20, 13, and 6.5 Cal/oz, as well as one feeding of distilled water. The volume of gastric contents was measured at 20-minute intervals by the double-aspiration technique using the marker polyethylene glycol 4000. Analysis of variance demonstrated a significant inhibition of gastric emptying related to increasing caloric density (P less than 0.001) when evaluated over the entire time of measurement. By 20 minutes, significant differences (P less than 0.01) were present between 0 and 6.5, 6.5 and 13, and 13 and 20 Cal/oz. A volume difference between 20 and 24 Cal/oz (P less than 0.05) was present only at 80 minutes. Despite the inhibition of emptying, higher caloric density feedings were associated with emptying of more calories over comparable periods (P less than 0.001). Regulation of gastric emptying by caloric density in premature infants is qualitatively similar to that in adults.