Denis R. Benjamin

Congenital posterolateral diaphragmatic hernia: associated malformations

Congenital posterolateral diaphragmatic hernia (CDH) is widely regarded as an isolated defect, but this view is incomplete. We reviewed our clinical and autopsy experience and the literature from the past 25 years in order to catalogue the frequency and clinical importance of additional malformations in patients with CDH. The study showed two broad categories of patients. In the larger group of infants (65 of 108, or 60%), CDH was the only severe defect, apart from those normally associated with the presence of abdominal viscera in the thorax. Thirty-six of these patients (55%) survived. A striking finding among infants with isolated CDH, not previously highlighted in the literature, was cryptorchidism which was present in 30% of males. By contrast, 43 patients (40%) had one or more severe extradiaphragmatic malformations; only six of these infants (14%) survived. Defects in morphogenesis were widespread, heterogeneous, and seemingly related to numerous pathogenetic mechanisms. Most often abnormalities involved the heart, brain, genitourinary system, craniofacial region, or limbs. The high incidence of multiple anomalies in some patients with CDH should influence our investigations into causes and mechanisms. Patients with CDH should be evaluated carefully for additional defects--their presence has a significant impact on management and worsens prognosis.

MUSHROOM POISONING IN INFANTS AND CHILDREN: THE AMANITA PANTHERINA/MUSCARIA GROUP

The clinical features and management of nine cases of mushroom poisoning due to Amanita pantherina (eight cases) and Amanita muscaria (one case) admitted to a childrens hospital are described. Most ingestions were in the toddler age group with males being more frequently involved. Symptoms occurred between 30-180 min with the onset of central nervous system depression, ataxia, waxing and waning obtundation, hallucinations, intermittent hysteria or hyperkinetic behavior. Vomiting was rare. Seizures or myoclonic twitching occurred in 4/9 patients, but was controlled with standard anticonvulsant therapy. No other anticholinergic or cholinergic signs were prominent. Recovery was rapid and complete in all patients.

Cholecystectomy is becoming an increasingly common operation in children

PURPOSE To determine the cause of a marked rise in cholecystectomy at a regional childrens hospital. METHODS Retrospective review of 185 patients undergoing cholecystectomy since 1984. The years 1984 to 1990 (group I) and 1991 to 1996 (group II) were compared. RESULTS Cholecystectomy for gallbladder disease increased from 4.4/year (group I) to 16.3/ year (group II). Abdominal ultrasound examinations increased during this time. The ratio of children diagnosed with gallstones and then undergoing cholecystectomy also increased (P = 0.005). In group 11, 43% of children had no apparent etiology for gallstones, and more children developed complications of gallstones and evidence of choledocholithiasis. CONCLUSIONS (1) The increased incidence of cholecystectomy is probably multifactorial. (2) Gallstone identification has increased owing to increased patient visits and more liberal use of ultrasonography in patients with abdominal pain. (3) More patients with cholelithiasis now undergo cholecystectomy perhaps because of a change in physician perception of the disease and an apparent increase in complications from gallstones.

Agenesis of the Mesencephalon and Metencephalon with Cerebellar Hypoplasia: Putative Mutation in the EN2 Gene—Report of 2 Cases in Early Infancy

Congenital absence of the midbrain and upper pons is a rare human malformation. We describe two unrelated infants with this anomaly and cerebellar hypoplasia who were born at term but died in early infancy from lack of central respiratory drive. MRI in both cases disclosed the lesions during life. Neuropathological examination, performed in one, included immunocytochemical studies of NeuN, synaptophysin, vimentin, and glial fibrillary acidic protein (GFAP). Autopsy revealed a thin midline cord passing through the clivus, in place of the midbrain; it corresponded to hypoplastic and fused corticospinal tracts with ectopic neural tissue in the surrounding leptomeninges. Some ectopia were immunoreactive for synaptophysin and NeuN and others were nonreactive. The neural surfaces facing the subarachnoid fluid-filled space left by the absent midbrain and upper pons were lined by an abnormal villous ependyma. The architecture of the cerebellar cortex was imperfect but generally normal, and Bergmann glial cells had normal radial processes shown by vimentin and GFAP. Structures of the telencephalon, diencephalon, lower brainstem, and spinal cord were generally well formed, but inferior olivary and dentate nuclei were rudimentary and the spinal central canal was dilated at lumbar levels. The cerebral cortex was normally laminated, but pyramidal neurons of layer 5 were sparse in the frontal lobes. The hippocampus, olfactory system, and corpus callosum were formed. An ectopic lingual thyroid was found and had been associated with hypothyroidism during life. A murine model resembling this dysgenesis is demonstrated by homozygous mutations of the organizer genes Wnt1 or En1, also resulting in cerebellar aplasia, and En2, associated with cerebellar hypoplasia. These genes are essential to the formation of the mesencephalic neuromere and rhombomere 1 (metencephalon or upper pons and cerebellum). Pax8 has binding sites in the promoter for En2 and is essential for thyroid development. We speculate that in the human, the failure to form a mesencephalon and metencephalon, with cerebellar hypoplasia, results from a mutation or deletion in the EN2 (Engrailed-2) gene.

Multicystic pancreatic hamartoma: a distinctive lesion with immunohistochemical and ultrastructural study.

A multicystic pancreatic hamartoma is reported in a 20-month-old female who presented with abdominal pain and distention. This appears to be a distinctive lesion not previously characterized in the English language literature. The 9-cm mass consisted of large, irregular lobules of well-formed pancreatic acini admixed with fibrous tissue and fat. Cystically dilated ducts of variable caliber lined by benign epithelium were present. Endocrine cell islets were not evident. Immunohistochemistry and ultrastructural examination illustrated insulin-producing cells diffusely throughout the exocrine tissue as single cells or in small groups. Cells producing other pancreatic hormones were markedly decreased when compared with an age-matched control pancreas and were similarly dispersed. The patient was alive and well without tumor 9 months later. This entity may provide an unusual opportunity for insight into pancreatic organogenesis and pancreatic cellular differentiation.

Absence of Immunoperoxidase Staining for Myoglobin in the Malignant Rhabdoid Tumor of the Kidney

Malignant rhabdoid tumor of the kidney, a clinically and pathologically unique tumor of early childhood, has been recently distinguished from nephroblastoma. Skeletal muscle histogenesis has been considered because of its aggressive course and histologic resemblance to rhabdomyosarcoma. Application of an indirect immunoperoxidase technique for myoglobin, an early marker of myogenesis, failed to show the protein in four malignant rhabdoid tumors of kidney. This substantiates the lack of ultrastructural evidence of skeletal muscle differentiation in these tumors.

Is the CSF lactate measurement useful in the management of children with suspected bacterial meningitis

The role of the cerebrospinal fluid lactate measurement was evaluated for the management of children with suspected bacterial meningitis. Although CSF lactate can be precisely measured, it provided no additional information over that which can be obtained from a CSF cell count. Reliance on the CSF lactate concentration alone would have increased the number of children being treated unnecessarily with antibiotics. There was neither clinical nor experimental evidence to suggest that the test should be used in the early diagnosis of meningitis. In patients with equivocal clinical and CSF findings, it failed to differentiate bacterial from nonbacterial infection. The data do not support the view that the measurement of CSF lactate has significant role in the management of children with suspected meningitis.

Bone marrow necrosis preceding acute lymphoblastic leukemia in childhood

Two patients who presented with bone marrow necrosis and eventually developed acute lymphocytic leukemia are reported, and similar cases in the literature are reviewed. Both patients responded to chemotherapy. Several possible mechanisms are discussed. Bone marrow necrosis appears to be another condition preceding acute lymphocytic leukemia in children. Cancer 52:2162‐2164, 1983.

Laboratory tests and nutritional assessment: protein-energy status

1. There is no one definitive laboratory test, group of tests, or indices that are satisfactory for the assessment of protein-calorie status. 2. Clinical evaluation remains the simplest, most widely available, most reproducible, and wisest method. It is satisfactory for the majority of clinical situations. 3. The laboratory should be used selectively and to complement clinical evaluation. Routine testing must be relegated to research protocols. 4. Always include some assessment of inflammation (for example, C-reactive protein, erythrosedimentation rate [ESR]), because its presence affects the interpretation of all the other tests. 5. The pathophysiologic effects of the underlying disease, especially in hospitalized patients, will affect the interpretation of every one of the laboratory tests. 6. Nutritional status often impacts more on the interpretation of commonly performed laboratory tests than laboratory tests impact on the assessment of nutrition.

Congenital Monocytic Leukemia: Report of a Case with Cutaneous Involvement, and Review of the Literature

Abstract: Congenital leukemia is a rare disease that can become manifest soon after birth. Cutaneous involvement consists of red, brown, or purple papules and nodules, and confluent areas of purpura. The diagnosis is established by the presence of leukemic cells in biopsy specimens of bone marrow and involved skin, and by immunocytochemical characterization of these cells. We report a case of congenital monocytic leukemia with a normal karyotype, whose disease underwent temporary spontaneous regression.