Case report: perianal necrotizing fasciitis in a near-term neonate.

Necrotizing fasciitis in the neonatal period is a rare, life-threatening condition. Previous cases of neonatal necrotizing fasciitis in the perianal region were speculated to have been initiated by rectal mucosal trauma secondary to rectal temperature measurements. We observed a case of fatal perianal necrotizing fasciitis in a neonate where the process began as a red ring surrounding the anus and guiac-positive stools, detected after a rectal temperature measurement. We speculate that the perianal necrotizing fasciitis that subsequently developed might have been initiated by a minor rectal mucosal injury, and we investigated the instrument used for the rectal temperature measurement to assess any potential areas on the probe sheath cover that might cause a minor injury. Each probe sheath cover examined had three areas that, in our opinion, could possibly generate a minor mucosal injury.

The immature platelet fraction: creating neonatal reference intervals and using these to categorize neonatal thrombocytopenias.

OBJECTIVE: The immature platelet fraction (IPF) is a laboratory measurement analogous to the reticulocyte count, but reflecting the thrombopoietic state. Similar to a reticulocyte count, it can be expressed as a percent (IPF%=percent of platelets that are immature) or as an absolute number per µl blood; the immature platelet count (IPC=IPF% × platelets per µl of blood). STUDY DESIGN: Using a retrospective analysis of de-identified data from non-thrombocytopenic neonates, we created reference intervals for IPF% and IPC. We then tested the value of these measurements for categorizing thrombocytopenic neonates. RESULTS: New charts display reference intervals for IPF% and IPC on the day of birth according to gestational age, and during the first 90 days after birth. Neonates with hyporegenerative varieties of thrombocytopenias (syndromes, small for gestational age, birth asphyxia) had lower IPF% and IPC than did neonates with consumptive thrombocytopenias (immune-mediated, infection, disseminated intravascular coagulation, necrotizing enterocolitis; both P<0.0001). CONCLUSION: The new reference interval charts can be used to recognize abnormal IPFs. The IPF parameters can help clarify the kinetic mechanism responsible for thrombocytopenias in neonates.

ETV6-NTRK3 gene fusions and trisomy 11 establish a histogenetic link between mesoblastic nephroma and congenital fibrosarcoma.

Congenital mesoblastic nephroma (CMN) is an infantile spindle cell tumor of the kidney that is subdivided into "classical" and "cellular" forms based on the degree of cellularity and mitotic activity. The histogenesis of CMN remains obscure, but relationships to other pediatric renal neoplasms have been proposed. However, cellular CMN is virtually identical histologically to congenital fibrosarcoma (CFS), a malignant tumor of fibroblasts in children of the same age group. Moreover, cytogenetic studies have reported common trisomies in CFS and cellular CMN, particularly of chromosome 11. We show here that t(12;15)(p13;q25)-associated ETV6-NTRK3 gene fusions described in CFS are also present in cellular CMN. ETV6-NTRK3 chimeric transcripts were detected in 8 of 9 cellular CMNs and 2 of 2 mixed CMNs. In contrast, all of the four classical CMNs tested were negative, as were cases of Wilms' tumor and clear cell sarcoma of the kidney. Moreover, we found trisomy 11 only in cellular or mixed CMNs with the ETV6-NTRK3 gene fusion. Our studies indicate that classical and cellular CMN have different genetic features and support the concept that cellular CMN is histogenetically related to CFS. They also provide insight into potential mechanisms involved in the transformation of the classical into the cellular form of CMN.

Concurrent Cushing's and Zollinger-Ellison syndromes in a patient with islet cell carcinoma. Case report and review of the literature.

This report documents the simultaneous occurrence of Cushing's and Zollinger-Ellison syndromes in a patient with islet cell carcinoma. The clinical concurrence of these two syndromes has been recorded in only three previous case studies, while three other case reports record evidence suggesting the presence of both gastrin and ACTH within the tumor but without clinical sequelae. In the present report, evidence based on multiple clinical and biochemical data supports the concept that both syndromes are a result of "ectopic" hormone production by the tumor.

Bilateral juvenile granulosa cell tumors in a 4-month-old dysmorphic infant. A clinical, histologic, and ultrastructural study.

Juvenile granulosa cell tumors were encountered within bilateral cystic ovarian masses in a 4-month-old infant. The child was the product of a consanguinous pregnancy, and manifested poor growth, relative microcephaly, facial asymmetry, and a malformed left ear. There was no history of gestational drug or hormone ingestion, and no evidence of abnormal endocrine activity after birth, however, the serum alpha-fetoprotein level was mildly elevated. The tumors were well defined by sonography and there was no evidence of metastasis. Histologically, a dense proliferation of round to oval tumor cells showed considerable individual cell necrosis and frequent microcyst formation. There was no evidence of luteinization and only mild nuclear pleomorphism. Immunoperoxidase study failed to reveal alpha-fetoprotein. Ultrastructural study supported the granulosa cell nature of the tumor, but a few cells contained bundles of intracytoplasmic filaments. There has been no evidence of recurrent disease during a 16-month follow-up period, and serial alpha-fetoprotein determinations have remained in the reference range. Comparison with two previously reported bilateral juvenile granulosa cell tumors suggests that this tumor occurs in young infants, and is amenable to conservative therapy.

Aprosencephaly and cerebellar dysgenesis in sibs.

Aprosencephaly is a rare, lethal malformation sequence of the central nervous system that has been attributed to a postneuralation encephaloclastic process. We describe autopsy findings consistent with aprosencephaly in 2 fetuses conceived from a consanguineous mating (first cousins). Both showed anencephalic manifestations; however, the crania were intact, with fused sutures. The neuropathologic findings were essentially identical. Each fetus had complete absence of the telecephalon and pyramidal tracts, rudimentary diencephalic and mesencephalic structures, primitive cerebellar hemispheres, posterolateral clusters of primitive neural cells in the medullas suggesting an abnormality of neural migration, a normally-formed spinal cord, and retinal dysplasia within normally-formed globes. In addition, both fetuses manifested a peculiar perivascular mesenchymal proliferation seen only within the central nervous system. The similarity of these cases, coupled with parental consanguinity, suggests a primary malformation in brain development due to the homozygous representation of a mutant allele. We hypothesize that these patients may represent a defect in a gene important in brain development, the nature of which has yet to be elucidated.

Xq28-linked noncompaction of the left ventricular myocardium: prenatal diagnosis and pathologic analysis of affected individuals.

Isolated noncompaction of the left ventricular myocardium (INVM) is characterized by the presence of numerous prominent trabeculations and deep intertrabecular recesses within the left ventricle, sometimes also affecting the right ventricle and interventricular septum. Familial occurrence of this disorder was described previously. We present a family in which 6 affected individuals demonstrated X-linked recessive inheritance of this trait. Affected relatives presented postnatally with left ventricular failure and arrhythmias, associated with the pathognomonic echocardiographic findings of INVM. The usual findings of Barth syndrome (neutropenia, growth retardation, elevated urinary organic acids, low carnitine levels, and mitochondrial abnormalities) were either absent or found inconsistently. Fetal echocardiograms obtained between 24-30 weeks of gestation in 3 of the affected males showed a dilated left ventricle in one heart, but were not otherwise diagnostic of INVM in any of the cases. Four of the affected individuals died during infancy, one is in cardiac failure at age 8 months, and one is alive following cardiac transplant at age 9 months. The hearts from infants who died or underwent transplantation appeared, on gross examination, to be enlarged, with coarse, deep ventricular trabeculations and prominent endocardial fibroelastosis. Histologically, there were loosely organized fascicles of myocytes in subepicardial and midmyocardial zones of both ventricles, and the myocytes showed thin, often angulated fibers with prominent central clearing and reduced numbers of filaments. Markedly elongated mitochondria were present in some ventricular myocytes from one specimen, but this finding was not reproducible. Genetic linkage analysis has localized INVM to the Xq28 region, where other myopathies with cardiac involvement have been located.

Pulmonary vascular resistance of children treated with nitrogen during early infancy.

BACKGROUND: We have empirically used supplemental nitrogen in newborns with a functional single ventricle and ductal-dependent systemic perfusion to prevent pulmonary vasodilation and deliver a greater proportion of flow to the systemic circulation. Thus, we reviewed patient outcome to determine whether adverse pulmonary vascular effects may be associated with this therapy. METHODS: From December 1991 to December 1995, the fraction of inspired oxygen was adjusted, with supplemental nitrogen if necessary, to maintain an oxygen saturation near 75% in 20 newborns awaiting heart transplantation. Medical records were reviewed to evaluate (1) the duration of nitrogen therapy, (2) pulmonary vascular histology, (3) postoperative pulmonary hemodynamics, and (4) survival. RESULTS: Thirteen patients underwent heart transplantation, 4 patients died without surgical intervention, and 3 patients underwent late aortic reconstruction. Supplemental nitrogen was used without exceeding a fraction of inspired oxygen of 0.21 for 38 +/- 6 days. One patient had evidence of changes of potentially irreversible pulmonary vascular disease. Pulmonary vascular resistance was not increased long-term in surviving patients. CONCLUSIONS: Supplemental nitrogen can be used to maintain a systemic oxygen saturation near 75% for an extended period in newborns with ductal-dependent systemic perfusion with no long-term adverse effect on pulmonary vascular resistance.

Differentiation of cholestatic jaundice in infants. Utility of diethyl-IDA.

Time-activity curves of technetium-labeled diethyl-IDA were used to evaluate 31 patients in an effort to differentiate infants with cholestatic jaundice. Results can be obtained rapidly with minimal radiation exposure and no known secondary effects. The combination of diethyl-IDA time-activity curves and gamma glutamyl transferase activity was found to discriminate biliary atresia from neonatal hepatitis. The group with neonatal hepatitis was characterized by abnormal, yet lower, gamma glutamyl transferase activities and diethyl-IDA time-activity curves which peaked within 1 minute of injection, yet decayed in a manner similar to cardiac activity. The group with biliary atresia was characterized by elevated gamma glutamyl transferase activities, hepatic peaks at 8 minutes and markedly delayed decay. In that early operative intervention is associated with increased survival in biliary atresia, prompt differentiation should improve prognosis.

Phaeohyphomycosis of the maxilloethmoid sinus caused by Drechslera spicifera: a new fungal pathogen.

"Phaeohyphomycosis" refers to soft tissue and systemic infections caused by dematiacious septate fungi. Drechslera spicifera, a dematiacious fungus, rarely pathogenic in humans was found to cause maxilloethmoid sinus disease in two immunocompetent children. The clinical presentation was similar to noninvasive aspergillosis. Intracavitary surgical excision without adjuvant chemotherapy resulted in apparent cure. The microbiologic and clinicopathologic aspects of this mycotic sinus disease are reviewed and discussed in relation to the entire spectrum of human disease reported which has been attributed to this organism.

Atelencephalic aprosencephaly.

Absence of the telencephalon and diencephalon characterizes the syndrome of aprosencephaly, while in atelencephaly, only the telencephalon is absent. Atelencephalic aprosencephaly is characterized by the presence of at least a rudimentary diencephalon. Embryologically, aprosencephaly is thought to occur after the optic vesicles form but before the cerebral vesicles appear. The syndrome is quite rare, with only 10 cases previously reported. We describe two fetuses with atelencephalic aprosencephaly. A 25-week estimated gestational age fetus was born to first-cousin parents and had a prenatal ultrasonographic diagnosis of anencephaly. The second, a 19-week estimated gestational age fetus, was thought to have semilobar holoprosencephaly by prenatal ultrasound. At autopsy, neuropathologic examination in both cases showed virtual absence of the cerebral hemispheres with an incomplete diencephalon. Microscopic examination in one case revealed disorganized neuropil with a proliferative vasculopathy. The optic globes were completely formed and attached to hypoplastic optic nerves, but retinal dysplasia was apparent histologically in both cases, and bilateral colobomata were present in one case. The findings in these cases demonstrate a spectrum of congenital variations that lie between the syndromes of atelencephaly and aprosencephaly, underscoring the complexity of the congenital anomalies.

Acute renal failure in idiopathic nephrotic syndrome.

Acute renal failure (ARF) associated with idiopathic nephrotic syndrome has been reported in adults with advanced age but is a rare event in children. We have reviewed the literature on this subject and report an additional pediatric case. The pathogenetic mechanisms which may lead to ARF during the course of idiopathic nephrotic syndrome are reviewed with a brief discussion of the role of angiotensin II and angiotensin converting enzyme inhibition in this setting. Although no consensus has emerged for the prevention and treatment of ARF in patients with nephrotic syndrome, a combination of salt-poor albumin and diuretics to reduce interstitial edema may be beneficial as a preventive measure. Once acute tubular necrosis is diagnosed, dialysis may be indicated. In the majority of reports the prognosis for recovery of renal function has been good even in patients in whom long-term dialysis was required.

The pediatric office laboratory. A look at recent trends.

The office laboratory has experienced an explosive growth in this decade as a result of technological advances and changes in reimbursement and regulatory practices. An evaluation of currently available methods, however, suggests that tests appropriate for the pediatric office laboratory today are similar to those recommended in a critical appraisal of pediatric laboratory medicine in 1974. This underscores the fact that the patient and not the technology dictates the tests to be performed.

Congenital chest wall mesenchymal hamartoma.

The case of an infant with mesenchymal hamartoma of the chest wall is presented, and the role of conservative diagnostic and therapeutic intervention is emphasized. A large mass that involved the right hemithorax and chest wall was detected in utero on routine ultrasonographic studies and diagnosed as mesenchymal hamartoma by percutaneous fine needle biopsy at 4 days after birth. The mass did not enlarge after birth, but surgical debulking was necessary at 1 month because of progressive respiratory compromise. Tumor regrowth was noted over the ensuing 8 months, and a second debulking at 9 months has been followed by a 6-year interval without evidence of recurrence.

Non-invasive vesicoureteral reflux detection: heating risk studies for a new device.

OBJECTIVE: To investigate a novel non-invasive device developed to warm bladder urine and to measure kidney temperature to detect vesicoureteral reflux. MATERIALS AND METHODS: Microwave antennas focused energy within the bladder. Phantom experiments measured the results. The heating protocol was optimized in an in-vivo porcine model, and then tested once, twice and three times consecutively in three pigs followed by pathologic examinations. RESULTS: Computer simulations showed a dual concentric conductor square slot antenna to be the best. Phantom studies revealed that this antenna easily heated a bladder phantom without over heating intervening layers. In-vivo a bladder heating protocol of 3 min with 30 W each to two adjacent antennas 45 s on 15 s off followed by 15 min of 15 s on and 45 s off was sufficient. When pigs were heated once, twice and three times with this heating protocol, pathologic examination of all tissues in the heated area showed no thermal changes. More intensive heating in the animal may have resulted in damage to muscle fibers in the anterior abdominal wall. CONCLUSIONS: Selective warming of bladder urine was successfully demonstrated in phantom and animals. Localized heating for this novel vesicoureteral reflux device requires low-power levels and should be safe for humans.

Discordant congenital malformations in monozygous twins: the amniotic band disruption complex.

A stillborn monozygous twin delivered after 26 weeks gestation manifested multiple severe anomalies in association with an aberrant band of amniotic membrane which attached to the fetus' head (exencephaly) and abdomen (gastroschisis), entangled his lower extremities (flexion contractures, atrophy and amputation of digitis) and fixed his body in a position of lateral flexion. He also had bilateral proptosis, lateral facial cleft, absence of the right kidney, and an imperforate anus. The other twin expired after 36 hours but autopsy disclosed no malformations. Discordancy in monozygous twins due to congenital malformations is well known, but has been noted only rarely in association with the amniotic band disruption complex (ABDC). comparison with previous reports shows that in all cases only one member of the twinship was affected. Furthermore, isolated limb lesions (constriction rings and amputations), which are more common manifestations of ABDC than severe eviscerations or craniofacial deformities, have not been reported in twins. These observations support the concept that the severe form of ABDC is an acquired intrauterine lesion and they suggest that isolated limb lesions may not be part of the same malformation complex.

Renal disease in adolescents with type I diabetes mellitus: a report of the Southwest Pediatric Nephrology Study Group.

Although 30% to 40% of patients with type I diabetes mellitus develop diabetic nephropathy, the usual signs of clinical nephropathy are often thought to be delayed until adulthood. We studied 13 adolescents with type I diabetes mellitus for 5 to 14 years who had renal biopsies completed because of clinical problems, including proteinuria, hematuria, or hematuria plus proteinuria. Changes typical of diabetes were seen by light and immunofluorescence microscopy; evidence of other renal diseases was not noted. On electron microscopy evaluation, glomerular basement membrane width was increased in 11 patients. In seven patients, mesangial volume was elevated above the normal range. Peripheral capillary filtration surface density was diminished below the normal range in five patients. Thus, several of these adolescents had severe glomerular lesions that were indicative of overt diabetic nephropathy. Within 2 to 3 years after biopsy, at least two patients were dialysis dependent. Thus, the adolescent diabetic patient with a relatively short duration of diabetes may be developing progressive diabetic renal lesions, and the clinical signs and symptoms at presentation may not be those typically seen in diabetic nephropathy.

Hepatic abscess in neonates.

Hepatic abscess in the neonatal period is a rare but serious disorder. To our knowledge, only 24 cases have been reported in the literature; this study presents 13 additional cases. The most common associated factors are sepsis, vessel cannulation, and abdominal surgery. The etiologic agent is variable. The abscess is usually multiple in the liver and involves other organs as well. In such instances, only supportive and vigorous antibiotic therapy can be offered. However, solitary liver abscess does occur, and this is theoretically amenable to surgical drainage. Thus, its recognition is of great importance.