Reference weights for placentas delivered before the 28th week of gestation.

CONTEXT: Very few studies have measured the weight of large numbers of placentas delivered before the 28th post-menstrual week. METHODS: We measured the weight of 930 singleton placentas delivered before the 28th post-menstrual week, and examined the distributions of weights in selected groups (week of gestation, reason for preterm birth, birth weight Z-score categories, placenta histology). We excluded 90 singleton placentas based on growth restriction as indicated by birth weight Z-score, resulting in a normative sample of 840 placentas. Weights for unfused twin placentas are also presented. RESULTS: Standard weights derived from our data set differ from those previously published, partly due to a larger sample size. Placenta weight varied with birth weight. Placentas from pregnancies ending due to preeclampsia, fetal indications or those showing evidence of poor perfusion on histology were among the smallest and their weights correlated with the smallest birth weights for gestational age. CONCLUSIONS: Placenta weights appear to be influenced by multiple maternal and fetal processes. We present a standard weight table for singleton placentas among live infants born between 23 and 27 completed weeks.

Post-transplant hypophosphatemia: Tertiary 'Hyper-Phosphatoninism'?

Hypophosphatemia is a common complication of kidney transplantation. Tertiary hyperparathyroidism has long been thought to be the etiology, but hypophosphatemia can occur despite low parathyroid hormone (PTH) levels and can persist after high PTH levels normalize. Furthermore, even in the setting of normal allograft function, hypophosphatemia, and hyperparathyroidism, calcitriol levels remain inappropriately low following transplantation, suggesting that mechanisms other than PTH contribute. Fibroblast growth factor-23 (FGF-23) induces phosphaturia, inhibits calcitriol synthesis, and accumulates in chronic kidney disease. We performed a prospective, longitudinal study of 27 living donor transplant recipients to test the hypotheses that excessive FGF-23 accounts for hypophosphatemia and decreased calcitriol levels following kidney transplantation. Hypophosphatemia <2.5 mg/dl developed in 85% of subjects, including one who had previously undergone parathyroidectomy; 37% developed phosphate < or =1.5 mg/dl. The mean pre-transplant FGF-23 level was 1,218+/-542 RU/ml. Within the first week following transplantation, mean levels decreased to 557+/-579 RU/ml, which were still above normal. FGF-23 was independently associated with serum phosphate (P < 0.01), urinary excretion of phosphate (P < 0.01), and calcitriol levels (P < 0.01); PTH was not independently associated with any of these parameters. We calculated area under the curve for FGF-23 and PTH between the pre- and first post-transplant levels as a summary measure of early exposure to these phosphaturic hormones. An area under the FGF-23 curve greater than the median was associated with a relative risk of developing hypophosphatemia < or =1.5 mg/dl of 5.3 (P = 0.02) compared with lower levels. Increased area under the PTH curve was not associated with greater risk of hypophosphatemia. Excessive FGF-23 exposure in the early post-transplant period appears to be more strongly associated with post-transplant hypophosphatemia than PTH.

Association of bronchopulmonary sequestration with expression of the homeobox protein Hoxb-5.

Bronchopulmonary sequestration (BPS) is caused by the abnormal development of an accessory lung diverticulum from the foregut very early in embryogenesis. The developmental abnormalities seen with BPS suggest that this anomaly is caused by abnormal expression of homeobox genes, which control axial identity and organ-specific patterning during embryogenesis. The authors previously have shown that the homeobox gene Hoxb-5 is necessary for normal airway branching during lung development. The authors now report that BPS is associated with aberrant developmental expression of Hoxb-5 protein, suggesting that this Hox gene is involved in the development of BPS.

Nitric oxide (NO.) stabilizes whereas nitrosonium (NO+) enhances filopodial outgrowth by rat retinal ganglion cells in vitro.

Recent observations suggest that nitric oxide (NO(.)) can increase or decrease growth cone motility. Here, these apparently paradoxical results are explained by distinct actions of different NO-related species. Filopodial morphology of 223 rat retinal ganglion cells was monitored under computer-enhanced video microscopy in the presence of NO synthase (NOS) substrates or inhibitors, donors of specific NO-related species, and membrane-permeant cyclic nucleotide analogs. Physiological NOS activity induced filopodial outgrowth, whereas inhibition of NOS stabilized filopodia. Similar to NOS, nitrosonium (NO(+) transfer) and peroxynitrite (ONOO(-)), which can regulate the activity of growth-associated proteins by S-nitrosylation and oxidation, respectively, induced filopodial outgrowth. In contrast, NO(.), which stimulates guanylate cyclase to increase cGMP, stabilized filopodial activity. Thus disparate NO-related species may offer a dynamic process of filopodial growth regulation.

Infantile G(M1) gangliosidosis: complete morphology and histochemistry of two autopsy cases, with particular reference to delayed central nervous system myelination.

Inborn metabolic errors causing lysosomal storage, such as beta-galactosidase deficiency (G(M1) gangliosidosis [G(M1)]), have well-recognized effects on cellular function and morphology. In some classically "neuronal" storage diseases, including G(M1), neuroradiologic observations of infants have suggested a delay in myelination on the basis of persistently "immature" signal intensities monitored over time. We sought to evaluate in a semiquantitative fashion the pattern and degree of myelination in two infantile G(M1) patients, one boy and one girl, autopsied at 15 months of age. We assigned myelination degrees for defined sites on an ordinal scale of 0 to 4, and compared them to published population-based values for autopsied infants. In both patients, earlier-myelinating structures were comparable in development to that expected for postconceptional age, whereas later-myelinating structures were delayed. These data correlate well with the neuroradiologic diagnosis of myelination delay in these infants and suggest that the metabolic defect has a primary influence on myelin development, in addition to effects related to neuronal storage. Furthermore, our analysis by light and electron microscopy and lectin histochemistry of both CNS and systemic tissues, several of which had not been described, add to the understanding of the stored material in different cell types.

Possible new autosomal recessive syndrome of lymphedema, hydroceles, atrial septal defect, and characteristic facial changes.

We describe two brothers with congenital lymphedema of lower limbs, atrial septal defect (ASD), and similar facial appearance. A sister had severe hydrops fetalis, ASD, omphalocele, and other anomalies. This combination of congenital lymphedema and ASD differs from other reported cases of congenital lymphedema and most likely constitutes a previously unrecognized autosomal recessive syndrome.

Desmoplastic small cell tumor: a report of three cases and a review of the literature.

PURPOSE: Desmoplastic round cell tumor (DSCT) is a highly malignant abdominal tumor first described in 1991, with subsequent cases predominantly noted in pathologic case reports. The authors evaluated response to alternating, intensive chemotherapy in three patients with DSCT, and reviewed the clinical experience with this newly described tumor as reported in the literature. PATIENTS AND METHODS: Three adolescent boys with DSCT were treated intravenously with vincristine 2 mg/m2, doxorubicin 75 mg/m2, cyclophosphamide 1.8 g/m2, alternating with 5-day cycles of etoposide 100 mg/m2/day, ifosfamide 1.8 g/m2/day for a total of 11-15 courses. RESULTS: Each patient showed initial tumor regression during chemotherapy, but developed progressive disease within 8-18 months. One patient subsequently showed a transient response to doxorubicin 45 mg/m2 plus 5-fluorouracil 500-600 mg/m2. All three patients died of disease within 20 months of diagnosis. A comprehensive literature review of clinical data on 101 reported cases of DSCT is presented. The median age was 21 years (range 6-38 years) with 78 male patients and 23 female patients. Ninety-nine cases involved tumor mass in the abdominal-pelvic cavity in proximity to the mesentery. Metastatic seeding to the omentum was most common, followed by spread of disease to liver, distant lymph nodes, lung, and occasionally to scrotum or to ovary. Tumor response to chemotherapy was noted in approximately 50% of 40 patients who received combinations of doxorubicin, cisplatin, cyclophosphamide, etoposide, and/or 5-fluorouracil. Four of 13 patients who received additional radiotherapy were alive at 24-48 months. Median survival was 17 months (range: 3-72 months), with only two patients reported disease free beyond 2 years at 40 and 48 months. CONCLUSION: DSCT should be included in the differential diagnosis of small round cell tumors in children and young adults. Tumor regression has been noted during multiagent chemotherapy, but prolonged survival is rare with current therapies.

IgA nephropathy as a possible cause of renal insufficiency following liver transplantation.

Three years following successful liver transplantation, a child developed proteinuria, hematuria and hypertension in the setting of progressive renal insufficiency. These abnormalities did not resolve with lower doses of ciclosporin. Because multiple drugs were required to control the hypertension and because no other etiology of the urinary abnormalities could be found, a renal biopsy was performed. The renal biopsy revealed findings consistent with severe IgA nephropathy, including glomerulosclerosis, segmental crescents, mesangial cell and matrix expansion, mesangial deposits, and positive immunofluorescence for IgA.

Polyneuropathies associated with IgM monoclonal gammopathies.

We studied ten patients with IgM monoclonal gammopathies. Five had M proteins that reacted with myelin-associated glycoprotein (MAG) and five had no recognizable antinerve activity. The neuropathy in the MAG-reactive patients was homogeneous by clinical and laboratory analysis, while the neuropathy in the MAG-nonreactive patients varied considerably. Both groups responded well to immunosuppressive therapy, which lowered the concentration of the serum M protein. The homogeneity of the MAG-reactive patients and their response to sustained lowering of the M protein levels support the concept that the IgM M protein directly damages nerve fibers and is the proximate cause of the polyneuropathy.

Atypical lymphohistiocytic infiltrate (pseudolymphoma) of the oral cavity.

In the oral cavity, differentiation between reactive and neoplastic lymphoproliferative lesions can, at times, be very difficult. We report an unusual case in which immunohistochemical findings were necessary to determine that the lesion was reactive despite the original interpretation of malignant lymphoma. The relationship of this lesion to atypical histiocytic granuloma, angiolymphoid hyperplasia with eosinophilia, and traumatic ulcerative granuloma with stromal eosinophilia is discussed and possible pathogenetic mechanisms are proposed. The value of immunohistochemistry in the diagnosis of extranodal lymphoproliferative lesions is emphasized.

Cystic medial necrosis in coarctation of the aorta: a potential factor contributing to adverse consequences observed after percutaneous balloon angioplasty of coarctation sites.

Percutaneous transluminal angioplasty has been shown to be both feasible and efficacious for the treatment of aortic coarctation. Recent reports, however, have indicated that the development of aortic aneurysms at or near the coarctation segment may complicate attempts to treat this lesion by catheter-based intervention. Accordingly, we examined the light microscopic features of coarctation segments excised at surgery (n = 31) or obtained at autopsy (n = 2) in 33 patients with coarctation of the aorta. Cystic medial necrosis, defined as depletion and disarray of elastic tissue, was observed in each of the 33 specimens. In the majority of coarctation specimens (22 of 33 or 67%) the extent of cystic medial necrosis, graded semiquantitatively on a scale of 0 (normal aorta) to 3+, was severe (3+). The finding that cystic medial necrosis represents a consistent histologic feature of coarctation of the aorta provides a pathologic basis for the formation of aneurysms observed after balloon angioplasty of coarctation sites.

Completely cartilaginous trachea in a child with Crouzon syndrome.

We describe a patient with Crouzon syndrome and congenital tracheal stenosis. The trachea lacked rings and was completely cartilaginous, making it rigid and narrow. The respiratory difficulties that are present in patients with Crouzon syndrome have been ascribed to the nasal or choanal defects that are associated with this condition. However, the presence of congenital tracheobronchial abnormalities as a cause of respiratory problems has not been widely investigated. Congenital tracheal stenosis may occur as an isolated defect or as one of many other congenital defects. In patients with Crouzon syndrome who have recurrent respiratory problems, congenital tracheal or bronchial defects should be considered since surgical intervention may correct the defect.

The child with peptic esophagitis: a correlation of radiologic signs with esophageal pathology.

Thirty-five children with gastroesophageal reflux were examined in a prospective study in which radiologic findings were correlated with the esophageal biopsy. No consistent radiologic abnormality was found in 24 children with minimal to moderate esophagitis and in three children with normal histology. Positive radiologic findings were found in five out of seven patients with severe, or severe ulcerative, esophagitis and in one child with moderate esophagitis. The positive radiologic findings consisted of signs of mucosal inflammation (mucosal edema, ulceration, esophageal narrowing) in five cases and abnormalities of esophageal function (aperistalsis, continuous reflux) in three. In children with peptic esophagitis, the barium examination of the esophagus appeared to be of diagnostic value only in the small number of patients with advanced disease; the absence of radiologic signs (with one exception) excluded severe inflammation. A statistically significant correlation was found between age and the histologic severity of esophagitis.