Possible serotonin syndrome in association with 5-HT(3) antagonist agents.

The serotonin syndrome results when serotonergic activity increases to abnormally high levels. It occurs with selective serotonin reuptake inhibitors (SSRIs), opioids, and other serotonergic agents when the serotonin system has been modulated by another serotonergic agent or compromised by illness. Although the symptoms are quite variable, the syndrome is characterized by a triad of altered mental status, neuromuscular abnormalities, and autonomic dysfunction. The authors report the probable occurrence of the serotonin syndrome with serotonin receptor subtype 3 (5-HT(3)) antagonist therapy when used to control nausea associated with chemotherapy in two seriously ill children. The first case involves combined use with mirtazapine and the second with fentanyl. These agents may pose a potential risk when used in such combination in seriously ill patients.

Case series: neuropsychiatric symptoms with pediatric systemic lupus erythematosus.

OBJECTIVE: To describe the psychiatric presentation, serologic findings, and neuroimaging patterns in children and adolescents with central nervous system involvement with systemic lupus erythematosus (CNS-SLE). METHOD: Pediatric patients with psychiatric symptoms who fulfilled the 1997 revised diagnostic American College of Rheumatology criteria for SLE were studied. Complement levels, and anti-double-stranded DNA, anti-Smith, anti-phospholipid, and anti-neuronal antibodies were evaluated. Computed tomography, magnetic resonance imaging, and single photon emission computed tomography (SPECT) neuroimaging studies were reviewed. RESULTS: The 10 patients with CNS-SLE presented with psychosis, mood disturbance, or confusion, and 8 patients had concomitant neurologic symptoms. The 8 girls and 2 boys ranged in age from 7.5 to 17 years. Serum anti-neuronal antibodies were positive with onset of symptoms and declined with improvement. Initial SPECT was abnormal in all 10 patients and remained abnormal. CONCLUSION: SPECT and anti-neuronal antibodies help confirm CNS involvement in patients with SLE and neuropsychiatric symptoms.

Cerebellar mutism in children: report of six cases and potential mechanisms.

Cerebellar mutism is a rare finding associated with resection of posterior fossa tumors or cerebellar hemorrhages. We reviewed the medical records of six children, aged 6 to 12 years, who developed cerebellar mutism after resection of a posterior fossa mass or as a result of posterior fossa trauma. From 1989 to 1994, 210 children underwent posterior fossa resection at our institution, and four developed mutism (an incidence of 1.6%). All four patients had primitive neuroectodermal tumors. The fifth patient experienced trauma, and another patient had an arteriovenous malformation (AVM). In four children, hydrocephalus developed as a result of their tumor or AVM. Four developed cerebellar mutism 24 to 48 hours after surgery or trauma, and one developed cerebellar mutism 5 days after surgery, coincident with hydrocephalus. In one, mutism occurred after a second resection was performed for a recurrence of his posterior fossa tumor. Cerebellar mutism lasted 10 days in one patient and 2 to 8 weeks in the other four. Dysarthria was apparent in four patients during the recovery phase. We suggest trauma to the dentate nucleus and/or its outflow tract, the superior cerebellar peduncle, as a cause of reversible mutism. Because posterior fossa tumors are common in children, mutism should be recognized as an important side effect of surgery.

Autopsy findings associated with neonatal hyperbilirubinemia.

Hyperbilirubinemia is associated with bilirubin deposition in tissue in the newborn including the liver, kidney, heart, adrenal, lung, and brain. High levels of serum bilirubin will stain the skin and sclera and be called "jaundice" clinically, and similarly high levels of bilirubin will stain tissues internally, preferentially in areas of tissue damage. Whether the bilirubin causes the damage or marks the damage because of other insults or both remains controversial.

Factors differentiating postponed neonatal death from survival in low birth weight infants.

Although survival of low birth weight infants during the neonatal period has improved, an increasing percentage of infants succumb after 28 days but before discharge from the nursery. In a retrospective study we compared 11 postponed neonatal deaths (PND) with survivors matched for birth weight, gestational age, gender, race, inborn or outborn status, and year of birth in an attempt to identify possible differentiating factors early in the clinical course. Evaluation of antenatal, intrauterine, and early nursery events could not differentiate the two groups. By day 14, however, significantly more PND required assisted ventilation because of poor respiratory effort and total parenteral nutrition because of poor gastrointestinal motility. Metabolic differences were noted at this time in the serum bilirubin, phosphorus, and chloride levels. At autopsy all infants had evidence of CNS injury, and moderate chronic lung disease, and in addition nine infants had bronchopneumonia. The major differences between the PNDs and survivors may primarily involve neurologic control of respiration and gastrointestinal motility. Early recognition of PND may have important medical, ethical, and financial implications for newborn intensive care.

Immunochemical and biochemical studies of human enamel proteins during neonatal development.

The present communication provides descriptions of the developmental, biochemical, and immunological properties of the human enamel extracellular matrix proteins. We report the isolation and partial characterization of the major human enamel proteins, the production of polyclonal antibodies directed against the human enamelins, and a comparison between the immunogenicity of enamelins and amelogenins from human and mouse enamel extracellular matrices. Our results indicate that although enamelins and amelogenins share some epitopes, each one of these proteins appears to invoke a different degree of immunogenicity.

Renal involvement in mixed connective tissue disease: a longitudinal clinicopathologic study.

Eleven of 30 patients with MCTD, followed for a mean of 10 years, developed immune complex nephropathy (five membranous, two mesangial, one mixed, and one sclerosing) with NS in nine of 11. Another patient had membranous nephropathy at autopsy. Patients with renal disease tended to have more systemic manifestations than those without. NS was at times of abrupt onset, recurrent, and/or persistent. Anti-RNP and serum complement were not helpful in predicting nephritis. Seventy-two percent of nephropathy and 62% of NS episodes resolved or improved after corticosteroid therapy. Five patients became hypertensive, two developed chronic renal failure and required chronic dialysis, and one needed acute dialysis twice. One patient progressed to focal proliferative crescentic nephritis with necrotizing arteritis. Three patients with nephropathy died, two of pulmonary hypertension with acute cor pulmonale and one of overwhelming sepsis. Nephropathy is relatively common in MCTD, is associated with substantial morbidity, and with the risk of hypertension and chronic renal failure.

Postponed neonatal death in the premature infant.

Improved obstetrical and neonatal care has increased survival for many small premature infants. However, there remains a distinct group who die of complications later in infancy. The autopsy findings associated with these "postponed neonatal deaths" were the subject of our retrospective study of 18 premature infants (mean estimated gestational age, 28.6 +/- 0.6 weeks) who survived from 4 weeks to 4 months of age (mean, 70 +/- 11 days). All 18 infants required prolonged artificial ventilatory support and parenteral nutrition. The major findings at autopsy were similar in all cases and included bronchopulmonary dysplasia, hepatic cholestasis and fibrosis, abnormalities of endochondral ossification, and diffuse cerebral gliosis and infarction. Infection was the most common cause of death, and most of the infants died with acute bronchopneumonia. These postponed neonatal deaths, while they do not appear in standard neonatal mortality statistics, represent a problem of concern.

Perinatal mortality associated with intrauterine infection due to pseudomonads.

Pseudomonads are common causes of nosocomial infections but are rarely implicated in perinatal disease. In a retrospective autopsy study we found that 9% of all acute congenital bacterial infections were due to Pseudomonas species. Premature rupture of membranes occurred in half the cases and clinical maternal amnionitis in two-thirds. One case was apparently nosocomial in origin. No known risk factors were implicated in any other case. Seven infants were stillborn and two died within a few hours. Congenital pneumonia, funisitis, and chorioamnionitis were found at autopsy. Intrauterine infection due to the pseudomonads poses a serious problem that has not been previously recognized.

Necropsy findings in neonatal asphyxiating thoracic dystrophy.

Asphyxiating thoracic dystrophy is an autosomal recessive disorder characterised by an abnormally small thorax, variable shortening of the extremities, and pelvic anomalies. Renal and pancreatic symptoms are found in longer survivors, although most cases die in infancy of respiratory failure. Seven neonatal cases were studied at necropsy. These cases ranged in gestational age from 32 to 40 weeks. One was stillborn and the other six survived from 1 hour to 10 days. Two were sibs born to consanguineous parents. Dwarfing was not pronounced and the extremities were shortened in only one infant who also had polydactyly. All seven showed visceral changes in addition to abnormalities of bone. Endochondral ossification was irregular in sections of femur, vertebra, and rib. Pulmonary hypoplasia was associated with the small thorax typical of this disorder. Periportal fibrosis and bile duct proliferation were seen in sections of liver, and in one case cirrhosis was found. Pancreatic fibrosis was variable. These necropsy findings correlate with later clinical manifestations of the disease and emphasise the multisystem nature of this disorder.

Brain injury and intrauterine death.

Many of the stresses contributing to brain injury in the intrapartum or neonatal period may also exist prenatally. To define this problem, we reviewed the clinical features and neuropathologic findings in 433 consecutive stillbirth autopsies. Twenty-five had evidence of periventricular/intraventricular hemorrhage or gliosis. Twenty infants had died in utero before active labor and five during delivery. Nine stillbirths were infected. Ten cases had periventricular/intraventricular hemorrhage alone, five had the hemorrhage with parenchymal hemorrhage, five had parenchymal hemorrhage only, and five had gliosis. This group of 25 cases establishes that intrauterine brain injury is not rare. Separation of antepartum events occurring in utero from those imposed during labor, delivery, resuscitation, and the neonatal period is very important and has significant medical and legal implications.

Dermal ultrastructure in leprosy.

We studied the ultrastructure of the dermal inflammatory response in 18 patients with leprosy. Biopsy specimens from 14 lepromatous patients, including four with Lucio's phenomenon and four with erythema nodosum leprosum, were compared with biopsy specimens from one borderline lepromatous and three borderline tuberculoid patients. In all, the dermal infiltrate consisted of macrophages, lymphocytes, and mast cells. This infiltrate was predominantly perivascular, and chronic reactive changes were found in the small dermal vessels. The macrophages contained phagocytized organisms within membrane-bound vacuoles and a wide variety of lysosomal residual dense bodies. Intraendothelial organisms were occasionally seen, especially in biopsy specimens from the patients with Lucio's phenomenon. The greatest number of mast cells were also seen in the infiltrate in those cases. The frequent close association of macrophages with lymphocytes and mast cells suggests an interrelationship between these cells that appears typical of the host response to leprosy.

Malformations associated with congenital absence of the gall bladder.

Thirty-four cases (29 children and five adults) of congenital absence of the gall bladder were found in a retrospective necropsy study. When the distribution of associated malformations in these patients was analysed, the cases were found to fall into several groups. The largest group (13) had multiple anomalies involving the genitourinary (83% reproductive tract, 42% renal), gastrointestinal (46% imperforate anus, 23% tracheo-oesophageal fistula), cardiovascular (54% cardiac defects, 23% single umbilical artery), and skeletal (31%) systems. Eight other patients had predominantly cardiac anomalies in addition to the agenesis of the gall bladder. Five had abnormalities associated with defects of the anterior abdominal wall. There were no additional malformations in the remaining cases. Family history was negative in all, suggesting a sporadic occurrence. Comparison with previously reported cases confirmed a similar distribution of anomalies. The hitherto unrecognised but consistent pattern of multiple malformations found with agenesis of the gall bladder may imply a non-random tendency for these defects to occur together.

A ten-year retrospective study of pink and yellow neonatal hyaline membrane disease.

Since it was first described several years ago, yellow bilirubin staining of the pulmonary membranes in neonatal hyaline membrane disease has apparently become more common. In a retrospective study of neonatal autopsy experience, it was found that as more of the premature infants survived longer, yellow hyaline membrane disease was a more frequent finding, increasing from 7% of all newborns having hyaline membrane disease at autopsy in 1970 to 50% in 1980. In comparing 499 cases with eosinophilic hyaline membranes with 168 cases of yellow membranes, newborns with bilirubin staining of the pulmonary membranes were found to be more premature (P less than .02), had smaller autopsy weight (P less than .002), and survived longer (P less than .00001). When multiple clinical parameters were compared between a group of infants with yellow membranes and a group of infants with pink membranes who were matched for gestational age, year of birth, and length of survival, no differences were found between the two groups. No correlation was found between kernicterus and yellow staining of the pulmonary hyaline membranes in the first years of the study, but there was a strong correlation in the last 5 years, coincident with the increase in the rate of yellow hyaline membrane disease found at autopsy. The gross bilirubin staining of the brain was the secondary type of kernicterus, not toxic bilirubin encephalopathy. The observation of bilirubin staining in the lung and in the brain correlates with prolonged survival in some very small premature infants. This does not appear to be a manifestation of bilirubin toxicity, but rather a marker of prior tissue damage.

Additional manifestations of the Neu-Laxova syndrome.

A newborn female with intrauterine growth retardation, bilateral cleft lip and palate, absent external nares and eyelids, low set ears, short contracted limbs, webbed digits, intestinal malrotation, and unilateral renal agenesis is reported. These multiple malformations are considered part of the Neu-Laxova syndrome.

Ultrastructure of the dermal microvasculature in leprosy.

Infection with M. leprae may lead to the presence of the organism within the dermal vascular endothelium, a phenomenon most pronounced in lepromatous leprosy. In order to study the ultrastructural features of the dermal microvasculature in leprosy, biopsies from 18 patients with lepromatous (14), borderline lepromatous (1) and borderline tuberculoid (3) leprosy were examined. Four patients with Lucio's phenomenon and four with erythema nodosum leprosum were included. The ultrastructural changes in the dermal microvasculature included endothelial swelling and hypertrophy, increased endothelial and pericytic cytoplasmic processes, and pronounced basal lamina reduplication. Occasional large, pale, endothelial cells with widely dispersed organelles were encountered. Phagocytized, membrane-bound intraendothelial organisms were found, similar in appearance to those within dermal macrophages. The predominantly perivascular dermal inflammatory infiltrate consisted of lymphocytes, macrophages and mast cells. The observed ultrastructural changes in the dermal microvasculature are similar to those previously described in the endoneurial vessels. While reflecting nonspecific responses of the dermal microvasculature in chronic inflammation, the findings support a possible role of the small dermal vessels in the chronic nature of the host's response to infection with M. leprae.