Synthesis and preliminary screening of N-ethyltryptamine derivatives related to reserpine and lysergic acid.
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Animals↗
Biomedical subjects
M Malone
Publications and source records attributed to M Malone.
Gains of chromosome 8 in pleuropulmonary blastomas of childhood.
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Chromosomes, Human, Pair 8↗
Extensive enteric leiomyolysis due to cytomegalovirus enterocolitis in vertically acquired human immunodeficiency virus infection in infants.
We report two infants with the acquired immunodeficiency syndrome (AIDS) and rectal bleeding due to cytomegalovirus (CMV) ileitis and colitis with minimal focal mucosal ulceration but with extensive leiomyolysis of the muscularis propria. Immunostaining and in situ hybridization for CMV showed numerous viral inclusions in the myocytes of the muscularis propria and vascular endothelium/smooth muscle with only occasional inclusions present in the muscularis mucosae. Colectomy was curative in one patient; in the other the bowel was only examined at postmortem.
Acquired Immunodeficiency Syndrome↗
Focal or diffuse lesions in persistent hyperinsulinemic hypoglycemia of infancy: concerns about interpretation of intraoperative frozen sections.
Persistent hyperinsulinemic hypoglycemia of infancy (PHHI) results from defects of regulated insulin release from pancreatic beta cells and is often refractory to medical treatment. Histological changes in the pancreas associated with PHHI may be focal or diffuse, and the intraoperative confirmation and siting of focal lesions would require frozen section diagnosis. The recognition of focal involvement and its distinction from diffuse disease by frozen section depends on the identification and distribution pattern of islet cells with large hyperchromatic nuclei. This study was designed to test the feasibility of using this parameter in PHHI to delineate focal from diffuse diseases prior to the introduction of frozen sections to guide intraoperative management in our institution. A total of 66 coded and randomized paraffin sections (from 18 PHHI and 4 postmortem pancreases) were scored by three independent observers into the following categories: a focal lesion (A), no large endocrine nuclei (B), few large endocrine nuclei (C), and frequent large endocrine nuclei (D). Interobserver concordance was complete in 88%, but there were minor discrepancies in the remaining 12%. When a focal lesion was present in one section no large endocrine nuclei were seen in sections from the rest of the pancreas. In four patients with diffuse PHHI, no or only very scanty large endocrine nuclei were seen. From this finding, and the observation that in other examples of diffuse disease, large endocrine nuclei were sparse even in large paraffin sections, we have reservations about using small frozen sections for reliable diagnosis.
Cell Division↗
Omenn's syndrome: differential diagnosis in infants with erythroderma and immunodeficiency.
The clinical differential diagnosis of erythroderma plus immunodeficiency and failure to thrive in neonates includes graft-versus-host-disease (GVHD), Omenn's syndrome (OS), and Netherton's syndrome (NS). In addition to immunological investigations, skin biopsy is an important part of the diagnostic work-up. We reviewed biopsies from 25 patients that were retrieved from the archives of the Department of Histopathology at Great Ormond Street, of which 9 were OS, 11 were GVHD, and 5 were NS. Five patients had two biopsy specimens. Both OS and GVHD show dyskeratosis and basal vacuolation. OS always shows acanthosis and almost always parakeratosis. GVHD shows a flat epidermis and rarely parakeratosis. OS and GVHD can be distinguished after immunohistochemistry for LCA and CD68 by the relative proportions of lymphocytes and macrophages in the dermal infiltrate (predominantly lymphocytes in OS, relatively more macrophages in GVHD). Skin biopsy diagnosis of OS is difficult before 6 weeks of age because the features are poorly developed. NS can be distinguished by psoriasiform acanthosis, thickening of the basement membrane, prominent dermal blood vessels, absence of dyskeratosis, and basal layer vacuolation, and a dermal infiltrate in which lymphocytes and macrophages are equally represented. Thus, the main difference between GVHD and OS is in the proportion of lymphocytes and macrophages in the infiltrate on immunohistochemical staining for LCA and CD68, while OS and NS may be distinguished on H&E morphology alone.
Adolescent↗
Diagnosis of neuronal ceroid lipofuscinosis (Batten disease) by electron microscopy in peripheral blood specimens.
Neuronal ceroid lipopofuscinosis (Batten disease, NCL) represents a group of common childhood neurodegenerative diseases with a shared feature of deposition of abnormal metabolic products in neurons and other tissues, including peripheral blood lymphocytes. In most forms of NCL no specific enzyme defect is known and the diagnosis relies primarily on ultrastructural identification of characteristic membrane-bound inclusions containing the abnormal metabolic product. All buffy-coat specimens examined during a 7-year period (1997-2004) for the exclusion or confirmation of the diagnosis NCL were reviewed. From a total of 265 samples, 9 were inadequate and NCL was diagnosed in 56. Five showed granular osmophilic deposits of infantile Batten disease (NCL1), 10 showed curvilinear profiles of classical late infantile Batten disease (NCL2), and 17 showed vacuolated lymphocytes with fingerprint profiles, indicating classical juvenile Batten disease (NCL3). 24 samples (43%) demonstrated compact electron-dense deposits with fingerprint profiles in the absence of vacuolated lymphocytes, indicative of variant forms NCL. Ultrastructual examination of peripheral blood allows reliable and specific diagnosis of subtypes of Batten disease, including variants, and is a useful, minimally invasive test for the diagnosis of NCL in childhood.
Ceroid↗
Massive cardiac chondroma presenting with heart failure and superior vena cava obstruction in a teenage boy.
Histologically benign soft-tissue chondromas have been reported at many anatomical sites but are an uncommon cause of soft tissue mass lesions in childhood, accounting for less than 1% of cases. The most frequent sites for extraosseous soft-tissue chondromas are the hands and feet. For the extremely rare visceral chondromas, the site can be lung, where they may represent a component of Carney's syndrome of extra-adrenal paraganglioma, pulmonary chondroma, and epithelioid leiomyosarcoma of the gastrointestinal tract. Primary cardiac chondromas are exceptionally rare in patients of any age although cardiac chondrosarcoma, both primary and metastatic, is well reported. We present a case of a teenage boy with a fatal cardiac chondroma
Adolescent↗
Isolated unilateral tuberous sclerosis-associated renal cystic disease in a neonate.
We present a male infant with antenatally detected, focal, unilateral apparently isolated renal cystic disease with morphological features of renal involvement in tuberous sclerosis. Only one previous case with similar presentation has been described. Most affected children present with either diffuse bilateral renal cystic disease or extrarenal manifestations. The major genes involved in tuberous sclerosis are now well described, and early onset of severe renal cystic disease in affected children often is related to the presence of a contiguous gene deletion syndrome involving TSC2 and PKD1 on chromosome 16.
Female↗
Melanotic neuroectodermal tumor of infancy: clinical, radiological, and pathological features.
We present a case of a 4-month-old female infant with a maxillary melanotic neuroectodermal tumor of infancy (MNTI) and review the pooled data from previous publications on this entity. The literature to date comprises 378 reported cases from 1918 to the present, from which data on the presence or absence of metastatic disease was available in 311, and on the presence or absence of local recurrence in 165. These pooled data suggest a local recurrence rate of 36% with metastasis occurring in 7% of cases. At present, the optimal management includes complete surgical excision with clear margins, but there are no reliable histopathological or molecular features to predict the biological behavior in individual cases.
Antigens, Neoplasm↗
Risk of germ cell malignancy in children with XY intersex versus isolated cryptorchidism by immunohistochemistry.
The risk of subsequent development of testicular germ cell neoplasia is related to presence of underlying developmental defects such as cryptorchidism, in which the risk is around 0.5%, and XY intersex with abdominal testes, in which the risk may be as high as 20-25%. We examined the hypothesis that the increased risk of germ cell malignancy in intersex testes with Y chromosome was a direct consequence of an abnormal increase in number of PLAP/CD117+ immature germ cells into postnatal life. Archival cases of uncomplicated cryptorchidism (CO) and XY intersex (INT) were identified and anonymized, and a subgroup of aged-matched cases had sections immunostained with placental alkaline phosphatase (PLAP) and CD117. From a total of 89 intersex and 105 cryptorchid cases identified, a power calculation to detect a 20% difference in expression between groups (alpha = 0.05, power = 80%) determined that 18 intersex and 36 cryptorchid cases were required. Thus, 58 cases were examined, median age 3 (range birth-11) years, including 39 CO and 19 INT. The prevalence of any PLAP+ germ cells was 2/39 (5.1%) versus 3/19 (15.7%), respectively. (Z = 1.4, p = 0.17). In contrast, 94% of cases showed presence of any CD117+ germ cells, but the frequency of CD117+ cells was not significantly different between groups (t = 0.56, p = 0.58). CD117 and PLAP identify different populations of germ cells in pediatric testes. The extent of increased risk of malignancy in XY INT is not simply related to increased numbers of immature PLAP+/CD117+ germ cells present; additional factors play a pathogenic role.
Adolescent↗
Histopathological features of testicular regression syndrome: relation to patient age and implications for management.
Testicular regression syndrome (TRS) represents a congenital condition in which no normal testicular tissue can be identified following exploration for a clinically impalpable testis. A spectrum of pathological findings may be present but there is little literature systematically examining these features. We searched a pediatric histopathology database to identify cases of TRS, and the histopathological findings were reviewed and pooled with those of all previously published smaller series. A total of 117 cases were identified during the period (1989-2004), median age 2 (range birth-12) years. In 52 (44%) a nodule was identified macroscopically, median maximum diameter 0.5 (range 0.1-2.0) cm. Microscopic hemosiderin-laden macrophages were present in 85 (73%), dystrophic calcification in 52 (44%), residual testicular tubules in 12 (10%), vas deferens in 71 (61%), and epididymal tissue in 39 (33%). The prevalence of hemosiderin laden macrophages and dystrophic calcification were significantly greater in cases < or =3 years (84% versus 64% and 55% versus 32%, respectively). But there was no significant difference in the frequency of other findings between the younger and older age groups; in particular, the presence of residual testicular tubules was similar (7% versus 13%, respectively). Furthermore, there was no significant correlation between identification of a macroscopically distinct nodule and presence of residual tubular structures, tubules being identified in 6 of the 65 cases in which no clearly identifiable nodule was seen macroscopically. The presence of hemosiderin-laden macrophages and foci of dystrophic calcification showed a positive association. TRS is associated with specific histopathological features, the findings being consistent with changes secondary to intrauterine testicular torsion. Residual testicular tubules are found in 10% of cases regardless of the presence or absence of a macroscopically identifiable nodule.
Age Factors↗
Congenital alveolar capillary dysplasia and associated gastrointestinal anomalies.
Congenital alveolar capillary dysplasia is a rare cause of irreversible pulmonary hypertension with 100% mortality. We present three cases of congenital alveolar capillary dysplasia with associated gastrointestinal abnormalities. Three full-term neonates presented with pulmonary hypertension needing ventilatory support by oscillation. Of the three, two neonates subsequently needed extracorporeal membrane oxygenation. Abdominal distension associated with bilious aspirates was the gastrointestinal manifestation. One child had duodenal atresia and anorectal anomaly, one with intestinal malrotation and the other with a rare combination of intestinal malrotaion and total colonic Hirschsprung's disease. All three infants succumbed to pulmonary hypertension at mean age 34 days. The etiopathogenesis and pathology of this condition are discussed with a comprehensive review of the literature.
Capillaries↗
Primary thoracic myxoid variant of extrarenal rhabdoid tumor in childhood.
Primary extrarenal rhabdoid tumors (RT) are now recognized as a specific entity in pediatric oncological pathology practice. We present an unusual case of a small cell myxoid variant of a thoracic RT in an infant and highlight the importance of recent molecular developments in the diagnosis of these tumors. An 8-month-old child presented with a short history of cough and shortness of breath. Imaging demonstrated a large mass occupying the majority of the thoracic cavity on the right side. A percutaneous needle biopsy of the mass showed fragments of tissue composed of malignant tumor with a predominant "small ovoid cell" phenotype and extensive myxoid change, with small nests and islands of tumor cells; occasional cells demonstrated open vesicular nuclei, prominent nucleoli, and eosinophilic cytoplasmic inclusions. Immunohistochemical staining revealed focal strong cytoplasmic positivity for cytokeratin, focal strong paranuclear cytoplasmic vimentin positivity, and INI1 staining showed normal nuclear positivity in control tissues but was negative in tumor cell nuclei. Electron microscopy demonstrated characteristic paranuclear whorls of intermediate filaments confirming the diagnosis of extrarenal malignant RT. The diagnosis of malignant rhabdoid tumor may be difficult, particularly in cases, such as the present, with a predominant small-cell myxoid phenotype. The characteristic expression patterns of cytokeratin and vimentin provide strong clues to the diagnosis, and the use of INI1 antibody now makes definitive diagnosis possible even on needle core biopsies.
Cell Nucleolus↗
Inherited ichthyoses: a review of the histology of the skin.
The histology of skin biopsies from 46 cases of different forms of congenital ichthyosis was reviewed. Sections were examined for hyperkeratosis, follicular keratosis, appearance of the granular layer, epidermal thickness, tonofilament clumps, epidermal vacuolation, spongiosis, bullae and dyskeratosis, appearance of the basal layer, inflammation, mitoses, and adnexae. A detailed description of the histological features of each type of ichtnyosis studied is presented. Some ichthyoses can be recognized on routine hematoxylin and eosin staining (bullous ichthyosiform erythroderma, Netherton's syndrome, and neutral lipid storage disease); some forms require frozen sections to demonstrate fat (neutral lipid storage disease) or enzyme activity (Sjögren-Larsson syndrome). Protein electrophoresis and enzymology are necessary for X-linked recessive ichthyosis. A close liaison with the clinicians is essential for the diagnosis of all types of ichthyosis, and combined studies including routine histopathology, electron microscopy, and frozen sections may be required for the diagnosis.
Humans↗
Pathology teach and tell: pediatric gastrointestinal stromal tumor.
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Adolescent↗
Adoptive transfer from interferon-alpha-fed mice is associated with inhibition of active experimental autoimmune encephalomyelitis by decreasing recipient tumor necrosis factor-alpha secretion.
Ingested type I interferon (IFN) suppresses clinical relapse in murine chronic experimental autoimmune encephalomyelitis (EAE), inhibits clinical attacks more effectively than subcutaneous doses, and decreases the adoptive transfer of EAE. To determine whether splenocytes from IFN-fed donors were "suppressor-like" populations, donor SJL/J mice were immunized and fed with mock IFN-alpha or with IFN-alpha every other day for at least 4 weeks after initial clinical attack. Recipients of adoptively transferred CD8+ T cells from mock IFN-alpha-fed donors showed no clinical improvement of clinical disease compared with actively immunized controls. In contrast, recipients of adoptively transferred CD8+ T cells from IFN-alpha-fed donors showed decreased clinical disease compared with recipients of mock IFN-alpha-fed CD8+ T cells. To evaluate the mechanism of protection by donor CD8+ T cells and to determine if ingested IFN-alpha activates natural immunomodulatory cell populations, the authors used the acute EAE model and naïve-fed donor animals as sources of T cells and CD8+ T cells. Con A-activated spleen T cells from naïve nonimmunized mock IFN-alpha-fed donors inhibited actively induced disease and showed decreased recipient TNF-alpha secretion compared with recipients of T cells from mock IFN-fed mice. Donor activated spleen CD8+ T cells from naïve nonimmunized IFN-alpha-fed animals suppressed actively induced EAE in recipients and showed decreased IFN-gamma and TNF-alpha proinflammatory secretion. Decreased recipient TNF-alpha secretion correlates best with the disease protection from IFN-fed T and CD8+ T cells.
Administration, Oral↗
Spontaneous remission of congenital leukemia: a case for conservative treatment.
A newborn infant with spontaneous remission of congenital leukemia cutis is described and a literature review of this uncommon phenomenon is provided. In view of the unusual and unpredictable behavior of this disease, chemotherapy should be withheld unless there is evidence of an 11q23 translocation or progressive disease. Otherwise, overall survival does not appear to be affected by adopting a conservative approach. Because of occasional late relapses, long-term follow-up is recommended. The biologic basis underlying spontaneous remission of congenital leukemia is unknown; therefore, molecular or molecular cytogenetic analysis of DNA obtained from a skin biopsy is recommended.
Biomarkers, Tumor↗
Cost and outcome analysis of home parenteral and enteral nutrition.
BACKGROUND: Previous estimates of the cost of home parenteral and enteral nutrition (HPEN) have excluded hospitalization costs or were conducted abroad and have limited applicability in the United States. Few studies have used validated measures to determine the effect of home nutrition support on quality of life. METHOD: A cost and clinical outcome analysis was performed by retrospective review of charts of patients receiving HPEN from 1991 to 1996. Questionnaires to determine the influence of therapy on lifestyle (n = 41) and a general health status questionnaire, the short form 36-item survey (n = 39), were mailed to patients. RESULTS: The annual cost per patient for parenteral solutions was $55,193 +/- 30,596 (mean +/- SD) based on Medicare charges and for enteral tube feedings was $9605 +/- 9327. The annual cost of hospitalization ranged from zero to $140,220 in the parenteral nutrition group and from zero to $39,204 in the enteral nutrition group. The annual number of hospitalizations per patient for patients receiving parenteral nutrition ranged from 0.52 to 1.10, compared with 0 to 0.50 in the enteral nutrition population. The health status of HPEN patients was significantly lower (p < .05) in five of the eight short-form 36 health domains compared with the general population. The areas of lifestyle most frequently affected were travel, sleep, exercise and leisure. CONCLUSIONS: The majority of the cost of therapy was associated with the direct provision of nutrition, although in some patients the hospitalization expenditure exceeded this cost. Home nutrition support had a significant negative impact on a patient's quality of life and lifestyle.
Adult↗