Dysmaturation in infants of mothers with myotonic dystrophy.

We examined the pathologic findings in four infants of mothers with myotonic dystrophy. Four of the anomalies present in these infants (nesidioblastosis, renal blastema, cryptorchidism, and patent ductus arteriosus) represent persistence of fetal organ structures or configurations. We suggest that a maturational defect may be present not only in muscle, but also in other tissues.

Immunocytochemical diagnosis of alpha-1-antitrypsin deficiency.

Eight cases of liver disease associated with alpha-1-antitrypsin deficiency are described. Six of the cases, including the only childhood case, showed no evidence of lung disease. An occult but variable clinical course is defined in this disorder. A spectrum in the severity of tissue change was noted, and in some instances, extensive liver disease was correlated with relatively minor derangement in liver function. While this form of liver disease is uncommon, it should be included in the differential diagnosis of adult liver disease. Screening for alpha-1-antitrypsin globules in periodic acid-Schiff stained liver tissue sections should be considered in certain cases of cryptogenic liver disease in adults, particularly when advanced disease presents suddenly, where micronodular (portal) cirrhosis is unrelated to excessive alcohol use, or where tissue changes exceed those anticipated from serum biochemical abnormalities. In most of these cases, tissue findings from liver biopsy or autopsy, rather than clinical suspicion, led to the diagnosis. The availability of a simple and reliable immunoperoxidase technique, applicable to routinely processed tissue samples, allowed for rapid and specific diagnosis in all cases. This immunocytochemical method has proven its usefulness in the prospective and retrospective tissue diagnosis of alpha-1-antitrypsin deficiency and associated liver disease.

Brief clinical report: an X-linked mental retardation syndrome with craniofacial abnormalities, microcephaly and club foot.

A male infant, who died of renal insufficiency at 6 months, had 2 similarly affected maternal uncles who died at 16 and 6 months respectively. Their manifestations include microcephaly, a large anterior fontanel, short nose with anteverted nostrils, club foot deformity, retarded psychomotor development and, in the index case only, kidney hypoplasia and dysplasia. The 2 obligatory carriers of this evidently X-linked recessive syndrome had no physical abnormalities.

Anomalies in an infant with Nager acrofacial dysostosis.

We report on an infant with Nager acrofacial dysostosis, laryngeal and epiglottic hypoplasia, abnormal septation of the right middle lobe of the lung, hypoplastic right first rib, and dislocation of the right hip. These findings suggest the possibility that patients with the Nager syndrome may have other developmental defects in addition to the facial and acral anomalies associated with this syndrome.

Postmortem manifestations of echovirus 11 sepsis in five newborn infants.

Five cases of fatal neonatal echovirus type 11 infection were observed in the Boston area during the summer and fall of 1979. Four of the mothers experienced gastroenteritis with fever and abdominal cramps late in the third trimester of pregnancy. The clinical course of each case was characterized by jaundice, hepatosplenomegaly, and progressive hepatic failure; all five infants were severely hypotonic. At autopsy massive hepatic and adrenal hemorrhage and necrosis, with evidence of consumption coagulopathy, were found. Echovirus type 11 was isolated from various sites before and after death. The histopathologic features and epidemiologic aspects of these cases are briefly discussed.

Villous adenoma of the urinary bladder: a morphologic or biologic entity?

Villous adenomas in the urinary bladder are rare neoplasms whose malignant potential is unclear. A case of a morphologically benign non-invasive mucin producing papillary neoplasm of the urinary bladder associated with cystitis glandularis is presented. Absence of A tissue isoantigen from the neoplastic and metaplastic cells and the presence of H tissue isoantigen in both neoplastic and metaplastic cells is observed in a patient whose blood type is A, indicating incomplete maturation of surface coat constituents. The histologically benign appearance of this lesion may belie a malignant potential.

Unusual sacrococcygeal embryologic malformations with cutaneous manifestations.

Two unusual sacrococcygeal neuroepithelial heterotopias manifested as masses associated with cutaneous signs. In a 13-month-old infant, a cystic coccygeal medullary vestige was associated with a midline epidermal nevus. In another patient, a lipomeningocele with neuroepithelial heterotopia manifested as a skin tag and mass in the right buttock. In both cases, the malformations probably resulted from abnormal canalization and retrograde differentiation of the distal neural tube. Cystic coccygeal medullary vestige results from dilation of a persistent ependymal cyst present commonly in neonates at the distal part of the coccyx. The lipomeningocele appears to have arisen from an aberrantly formed ependymal canal. The embryologic events that gave rise to the lesions, the differential diagnosis of postrectal masses, and the common association of midline lesions of skin and soft tissue with neural defects are stressed.

Infantile polycystic disease of the liver and kidneys.

Kidney and liver tissue from eleven patients with recessively inherited infantile polycystic disease (IPCD) were examined to document the extent of renal tubular cyst formation and hepatic fibrosis, to assess survival, and to examine the usefulness of current classifications. Four infants with 90% or more cystic renal change did not survive beyond twenty days. In contrast five of the seven less severely diseased patients with a 20-75% range of cystic change are still alive at six to twenty-one years of age. Liver samples showed hamartomatous bile duct proliferation in all patients studied with the most prominent portal fibrosis in the oldest patient. In both families with two affected siblings, the clinical course and pathological expression of renal disease were dissimilar. Tissue analysis from these cases is consistent with the idea that IPCD has a spectrum of phenotypic expression with prognostic implications from tissue diagnosis in the individual patient, but not necessarily as four genetically determined rigidly defined subgroups. It is concluded that each affected child with IPCD must be evaluated separately.

Wilms' tumor of the endocervix.

We report a case of primary Wilms' tumor of the endocervix in a 13-year-old girl. The tumor was polypoid, filled the vagina, and was attached to the endocervix by a stalk. Microscopic examination disclosed blastematous, epithelial, and stromal elements characteristic of Wilms' tumor. The patient's kidneys were normal on intravenous pyelographic examination and on palpation at laparotomy, and she has remained free of disease for 9.6 years after hysterectomy.

Fatal pulmonary embolism following removal of a central venous catheter.

A 1-year-old child developed fatal septic pulmonary embolism upon removal of a central intravenous catheter. Histologically identical material was found in the pulmonary arteries and in the inferior vena cava at the catheter tip site. The pathophysiology of pulmonary embolism occurring during childhood is reviewed.

Fatal postoperative acute appendicitis in a neonate with congenital heart disease.

Acute appendicitis with perforation is almost unknown in the first week of life. We present a 7-day-old male infant with the hypoplastic right heart syndrome and clinically unsuspected acute appendicitis who died 7 days after the successful creation of a Waterston shunt.

Epstein-Barr viral hepatitis: an unusual case and review of the literature.

We report a patient with icteric hepatitis and abdominal pain caused by Epstein-Barr virus in the absence of other common features of infectious mononucleosis. The peak alanine aminotransferase was 289 IU/I. Hemolytic anemia and urinary retention complicated the patient's course. Patients with infectious mononucleosis commonly have hepatic involvement but isolated symptomatic hepatitis is unusual. Although rare cases of liver failure have been reported, there is no evidence that Epstein Barr virus causes chronic liver disease. The clinical and histological features of Epstein Barr virus-induced hepatitis are reviewed.

Villous adenoma of the duct of Wirsung.

A patient presenting with recurrent pancreatitis was found to have a benign polypoid villous adenoma of the duct of Wirsung. The tumor was excised locally via transduodenal access to the duct. The patient has now remained free of pancreatitis for 24 months. Obstruction of the pancreatic duct by this rare tumor appears to have been the cause of pancreatitis. Villous adenomas of the pancreatic duct epithelium may be premalignant.

Primary hepatocellular carcinoma following nonspecific non-B hepatitis with tumor DNA negative for HBV DNA.

An association between non-A, non-B hepatitis and hepatocellular carcinoma has been made on the basis of negative serological markers for hepatitis B virus (HBV); however, hepatocellular carcinomas have been found to contain hepatitis B virus deoxyribonucleic acid (HBV DNA) in individuals who lack serological markers of HBV infection. Therefore, reports which ascribed a hepatocellular carcinoma to non-A, non-B hepatitis but did not examine the tumor for HBV DNA are open to question. We describe a case of chronic active hepatitis with primary hepatocellular carcinoma that lacked HBV DNA in the tumor, the nontumorous liver tissue, and serum. The individual lacked all serological markers for HBV infection. This report more fairly supports the association between hepatocellular carcinoma and chronic hepatitis not due to hepatitis B. Whether this is related specifically to a non-A, non-B hepatitis agent requires identification of the viral agents that cause non-A, non-B hepatitis.

Spinal cord infarction following therapeutic renal artery embolization.

A patient with dialysis cachexia became paraparetic within hours of therapeutic renal artery embolization. At autopsy, emboli of absorbable gelatin sponge filled spinal arteries, accompanied by spinal cord infarcts. The renal arteries of patients with end-stage renal disease are smaller than normal becaue of intimal fibrosis associated with prolonged dialysis. Embolic material can reflux more readily in these patients than in patients with renal tumors.

Simultaneous occurrence of hepatic adenoma and focal nodular hyperplasia: report of a case and review of the literature.

We report the case of a 28-year-old woman with a history of oral contraceptive use and the simultaneous occurrence of histologically proven hepatic adenoma and focal nodular hyperplasia. A review of the literature discloses that the simultaneous occurrence of these hepatic lesions is a rare event. Epidemiologic evidence suggests that hepatic adenomas are etiologically related to oral contraceptive use, whereas focal nodular hyperplasia does not seem to be caused by these agents. The finding of the two lesions in the same liver may represent the chance occurrence of two rare diseases.

Mesenteric oxygen metabolism, ileal mucosal hydrogen ion concentration, and tissue edema after crystalloid or colloid resuscitation in porcine endotoxic shock: comparison of Ringer's lactate and 6% hetastarch.

We performed an experimental trial comparing crystalloid (Ringer's lactate) and colloid (hetastarch) resuscitation in pentobarbital-anesthetized pigs. Superior mesenteric arterial blood flow (Qsma) was measured using an ultrasonic flow probe, and ileal intramucosal hydrogen ion concentration [( H+]I) was estimated tonometrically. Beginning at t = 0 min, all animals were infused over 20 min with Escherichia coli (0111:B4) lipopolysaccharide (LPS; 150 micrograms/kg). Starting at t = 0 min and continuing for the duration of the experiment (3 hr), pigs in group I (N = 9) were resuscitated with Ringer's lactate (1.2 ml/kg min), whereas animals in group II (n = 9) were infused with 6% hetastarch in saline (0.4 ml/kg min). Systemic and mesenteric hemodynamic changes induced by LPS were similar in both groups; mean arterial pressure and systemic vascular resistance index decreased (P less than .05), but cardiac index was well preserved. Central venous pressure increased (P less than .05). Superior mesenteric O2 delivery decreased significantly (P less than .05) in both groups, although mesenteric O2 uptake was unchanged. Ileal [H+]I increased (P less than .05) in both groups. Gravimetrically determined extravascular water was greater in lung (P = .03) and ileum (P = .058) in group I as compared to group II. Although crystalloid infusion was associated with greater tissue edema, this effect did not translate into a difference in systemic or regional (i.e., mesenteric) O2 uptake or greater ileal tissue acidosis.

Electron microscopy of Hodgkin's disease tissue cultures.

Cells from 9 monolayer tissue cultures prepared from Hodgkin's disease tumors in the spleen were examined in the electron microscope. Three established culture lines (carried in vitro for greater than 3 years and passaged greater than 200 times) that contained aneuploid karyotypes were composed of oval cells with numerous interdigitating surface microvilli. The nuclei were complex and convoluted with multiple large nucleoli and dispersed chromatin. The cytoplasm contained lysosomes, microfilaments, a complex Golgi apparatus, nondilated rough endoplasmic reticulum, polyribosomes, fat, and glycogen. One Hodgkin's disease monolayer with aneuploid chromosomes examined from the 4th to 48th passage in culture was composed of larger cells with fewer microvilli and numerous multinuclear giant cells. Two monolayers derived from transplanted tumors in nude mice inoculated with Hodgkin's disease cultured cells were similar to the original cell lines. The ultrastructural features of these 6 cultures with aneuploid karyotypes differed from those of 3 monolayers which, although prepared from Hodgkin's disease splenic tumors, were composed of fibroblastic cells with diploid chromosomes. The aneuploid Hodgkin's disease cultures did not resemble 6 normal spleen, thymus, or lung monolayers, Raji lymphoblastoid suspension cultures, or Hela cells. Our electron microscopic studies indicate that adherent cells which replicate in some monolayer tissue cultures derived from Hodgkin's disease tumors are related to and possibly derived from neoplastic macrophages.

Myopericarditis and enhanced dystrophic cardiac calcification in murine cytomegalovirus infection.

In mice inoculated with murine cytomegalovirus (MCMV) an acute myopericarditis developed which varied from a focal lymphohistiocytic inflammation to intense inflammation with necrosis and cytomegalic inclusion-bearing cells. Sublethal doses caused focal transient nonspecific chronic inflammation, followed months later by an increased frequency and extent of dystrophic cardiac calcification. When such latently infected hearts were heterotopically transplanted into uninfected animals which were then immunosuppressed (IS), a fatal generalized CMV infection followed. Cytomegalic inclusion-bearing endothelial, fibroblastic, and myocardial cells were seen in the intense inflammation found in hearts taken from mice 4 days after lethal inoculation and transplanted into uninfected mice, which were then IS. These findings may be relevant to human cardiac transplantation because they show that MCMV regularly causes cardiac infection with both acute and chronic consequences; chronic injury may follow a morphologically nonspecific myopericarditis which might not be attributed to CMV infection.

Hepatic dysfunction as the presenting feature of acute lymphoblastic leukemia.

PURPOSE: Hepatic dysfunction is a rare presentation of leukemia in children. Because most chemotherapy agents are metabolized by the liver, this complication may have major adverse consequences and effective treatment could be compromised. PATIENTS AND METHODS: The MEDLINE database and current management guidelines from the United States Pediatric Cooperative Cancer Groups were reviewed and analyzed. Data from two institutional cases are described. RESULTS: Although previous literature is not informative, our experience suggests that children with leukemia and moderate hepatic dysfunction may tolerate aggressive chemotherapy. CONCLUSION: Current protocol guidelines for dose modification for liver disease may be overly stringent and modification may be beneficial.