Search PubMed⌕ Search

Biomedical subjects

S J Qualman

Publications and source records attributed to S J Qualman.

At least 37 records · Page 2Linked to original sources
PubMed1998

Pediatric bronchioloalveolar carcinoma: a favorable pediatric malignancy?

Primary pulmonary tumors are infrequent in children. Bronchioloalveolar carcinoma has been documented rarely in the pediatric population. Before this report, there have been only three cases of bronchioloalveolar carcinoma in patients less than 16 years of age. Our two cases represent two of the youngest cases (ages 6 and 15 years) reported with bronchioloalveolar carcinoma. They illustrate many of the typical findings of this disease including clinical presentation, diagnostic difficulty, and better prognosis compared with other pulmonary malignancies. This neoplasm appears to have a favorable outcome in childhood.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMed1997

Undifferentiated sarcomas of children: pathology and clinical behavior--an Intergroup Rhabdomyosarcoma study.

Undifferentiated soft tissue sarcoma (UND-STS) is the most poorly defined tumor eligible for intergroup Rhabdomyosarcoma Studies (IRS). Recent IRS UND-STS experience was reviewed to assess the histologic characteristics and clinical behavior of undifferentiated sarcomas. Of the 1,527 patients entered on IRS-III and IRS pilot-IV, 96 had tumors classified by the IRS Pathology Committee as UND-STS. Of these, 52 had adequate histologic material for this study. After application of immunohistochemistry, 18 tumors were reclassified, mostly as embryonal rhabdomyosarcomas (RMS), primitive neuroectodermal tumors, and intraabdominal desmoplastic small found cell tumors. The remaining 34 UND-STS had a diffuse hypercellular histologic pattern made up of sheets of medium-sized cells. The tumor cells had a minimal to moderate amount of cytoplasm and a variable nuclear morphology, predominately vesicular with finely granular chromatin. Except for reactivity with antibodies against vimentin, most tumors had a negative immunohistochemical profile. The 5 year Kaplan-Meier survival estimate for patients with non-metastatic disease was 72%, a significant improvement when contrasted with patients diagnosed to have UND-STS in IRS-I and IRS-II.

Adolescent↗
PubMed1996

Disseminated neuroblastoma in the nude rat. A xenograft model of human malignancy.

BACKGROUND: The overall survival of children with neuroblastoma remains less than 30% due to disease dissemination at the time of diagnosis. An animal model of neuroblastoma, with characteristics similar to those observed clinically in children, would be beneficial to investigations into the diverse biology of this tumor. The purpose of this study was (1) to develop a model of disseminated neuroblastoma in the nude rat by intracardiac injection of neuroblastoma cells derived from cell lines with different N-myc copy numbers; (2) to investigate the effect of age on tumor growth and dissemination; and (3) to assess progression of disease radiologically and correlate with autopsy findings. METHODS: Nude rats (n = 38), 5-13 weeks of age, underwent intracardiac injection of the human neuroblastoma cell lines IMR-32 with amplified N-myc oncogene and SKNSH with 1 N-myc copy. The animals were observed for at least six weeks for the development of tumor. Twelve rodents injected with IMR-32 cells underwent imaging studies including magnetic resonance imaging (MRI), skeletal radiographs, and indium-111(IN-111)-diethylenetriamine penta-acetic acid-D-Phe1-octreotide scintigraphy. Autopsies with standardized microscopic examinations were performed on all animals. RESULTS: Most of the nude rats (95%) developed neuroblastoma following intracardiac injection of neoplastic cells. Disseminated tumor was evident in 66% of animals. Anatomic sites of neuroblastoma growth were similar to those observed clinically in children, including adrenal glands, paraspinal ganglia, bone, bone marrow, and skin, but no tumor was identified in the liver. Disseminated disease occurred in more animals injected with IMR-32 (78% of animals) than with SKNSH cells (34% of animals) (P < 0.05). Tumor spread appeared to be age dependent; only rodents 5-8 weeks old at the time of injection developed disseminated disease when compared with animals 9 weeks of age or older (P < 0.0001). Radioreceptor scintigraphy demonstrated only pericardial tumor; MRI identified pericardial, adrenal gland, and subcutaneous neoplasms; only skeletal radiographs detected neuroblastoma in cortical bone. CONCLUSIONS: (1) Following intracardiac injection of human neuroblastoma cell lines into nude rats, a xenograft model of disseminated disease develops that closely parallels the malignant process in children. (2) Tumor dissemination is associated with the cell line that demonstrates N-myc amplification and with young age of the recipient at the time of injection. (3) Tumor growth and dissemination may be assessed radiologically. (4) This model of human malignancy may offer an opportunity to investigate the pathophysiologic mechanisms underlying tumor development and dissemination in advanced stage neuroblastoma.

Age Factors↗
PubMed1996

Ménétrier disease of childhood: role of cytomegalovirus and transforming growth factor alpha.

OBJECTIVE: Because the role of cytomegalovirus in Ménétrier disease in children remains unclear and recent studies have implicated transforming growth factor alpha in the pathogenesis of this disease in adults, we investigated the possibilities that (1) cytomegalovirus is etiologic in Ménétrier disease in children and (2) transforming growth factor alpha mediates its development. METHODS: The presence of a cytomegaloviral infection and the pattern of transforming growth factor alpha immunolocalization were determined in the gastric mucosa of four pediatric patients with Ménétrier disease, in control subjects (children with normal gastric mucosa, gastritis, or prostaglandin E1-induced antral hyperplasia), and in adults with Ménétrier disease. RESULTS: Evidence of a cytomegaloviral infection was present only in the four children with Ménétrier disease. The pattern of transforming growth factor alpha immunostaining was identical in the specimens from pediatric and adult patients with Ménétrier disease. This pattern was distinct from that found in the pediatric control specimens. CONCLUSIONS: These data strengthen the possibilities that cytomegalovirus is etiologic in children and that transforming growth factor alpha is involved in the pathogenesis of Ménétrier disease in both children and adults.

Adult↗
PubMed1996

Identification of a duplicated undescended testicle (polyorchia): an unexpected benefit of laparoscopic localization.

Polyorchidism is an uncommon anomaly resulting from transverse division of the embryonic genital ridge. Up to 50 percent of cases are associated with cryptorchidism. The present case describes a 6-year-old boy who was referred for evaluation of an undescended right testicle. Examination revealed compensatory hypertrophy of the left testis (2 cm length; 2 cc volume; volume twice normal for age). These measurements were consistent with the presence of monorchidism rather than cryptorchidism. Laparoscopy was performed to confirm the absence of the nonpalpable testicle and to localize any testicular remnants. Laparoscopic findings included a hypoplastic testicle at the mid lumbar it level (abdominal testis) and a second hypoplastic testicle just distal to the internal inguinal ring (inguinal testis). Both measured no more than 1 cm in greatest diameter and were excised laparoscopically. Histologic examination revealed two immature tests, with the abdominal testis demonstrating atrophy. It is well recognized that laparoscopy the high undescended testicle, or identification of testicular remnants. In addition, nonpalpable testicle assists in localization of the undescended testicle or identification of the testicular remnants. In addition,laparoscopic high ligation and division of the gonadal vessels can be performed in cases of the high undescended testicle. Moreover, as demonstrated here, laparoscopy may also allow identification of polyorchia, especially in cases where the proximal testicle is intraabdominal. Inguinal exploration alone may result in failure to recognize a higher duplicated gonad. Failure to recognize and excise the duplicated, potentially dysplastic testicle may place the child at risk for subsequent malignant degeneration.

Child↗
PubMed1995

Intraoperative detection and resection of occult neuroblastoma: a technique exploiting somatostatin receptor expression.

Tumor cell expression of specific high-affinity somatostatin receptors has been associated with a favorable prognosis in children with neuroblastoma. The purpose of this study was (1) to document intraoperatively the in vivo binding of the somatostatin analogue 125I-tyr3-octreotide to high-affinity somatostatin receptors expressed on human neuroblastoma, using a hand-held gamma detector; (2) to determine whether gamma-probe detection of radioligand binding to tumor receptors could identify occult malignancy; and (3) to determine the safety and biodistribution of 125I-tyr3-octreotide in children. Six children with stage III or IV neuroblastoma received an intravenous injection of 125I-tyr3-octreotide and underwent operative exploration using gamma-probe detection of radioligand binding to tumor somatostatin receptors. Tissue that demonstrated in vivo binding of 125I-tyr3-octreotide, or that was suspicious for tumor, was extirpated and analyzed by histopathology, immunohistochemistry, and microautoradiography. The biodistribution of 125I-tyr3-octreotide was recorded intraoperatively over time. Tumor tissue from each child also was assayed in vitro for somatostatin receptor expression by competitive binding studies using 125I-tyr3-octreotide. In vivo binding of 125I-tyr3-octreotide to malignant tissue was documented in the five children with a known tumor burden. Seventeen sites of radioreceptor binding were amenable to resection. Histopathological analysis confirmed neuroblastoma in 15 of these specimens. Four of the 15 proven tumor foci were occult malignancies. Every site of histologically proven neuroblastoma demonstrated in vivo binding of 125I-tyr3-octreotide. Five of seven sites histologically negative for neuroblastoma also were negative for in vivo radioreceptor binding. Microautoradiography confirmed in vivo binding of 125I-tyr3-octreotide to tumor cells. Uptake of 125I-tyr3-octreotide in abdominal organs occurred within 15 minutes of injection, was highest in the liver and gallbladder, and decreased over 24 hours. The conclusions were as follows. (1) 125I-tyr3-octreotide binds, in vivo, to somatostatin receptors on neuroblastoma, with 100% sensitivity and 71% specificity. (2) Occult neuroblastoma is found through gamma-probe detection of radioligand binding to receptors. (2) The biodistribution of 125I-tyr3-octreotide reflects the hepatobiliary clearance of this radionuclide. (4) Radioreceptor-guided surgery may safely provide more complete operative staging and cytoreduction of neuroblastoma.

Biomarkers, Tumor↗
PubMed1995

Pseudosarcomatous myofibroblastic tumor of the urinary bladder in children: a study of 11 cases with review of the literature. An Intergroup Rhabdomyosarcoma Study.

Pseudosarcomatous myofibroblastic tumor (PMT) is the result of reactive proliferation of myofibroblasts. In children, PMT of the urinary bladder can be mistaken for embryonal rhabdomyosarcoma clinically, radiologically, and by light microscopy. We are reporting the clinical, histological, and immunohistological features of 11 patients with childhood PMT of urinary bladder that were diagnosed initially as a sarcoma, usually rhabdomyosarcoma. The morphologic spectrum of PMT is broad, with mixtures of myxoid, leiomyomatous, and sclerosing matrix patterns, the myxoid type being the most common. The proliferating cells consist of three forms of myofibroblastic cells: long spindle cells (type I), intermediate spindle cells (type II), and ganglion-like cells (type III), together with various types of inflammatory cells. The immunohistologic profile of the proliferating cells was characterized by positive reactions to vimentin, muscle-specific actin, alpha-smooth-muscle actin, polyclonal desmin, and keratin. Ultrastructural studies showed myofibroblastic differentiation of the tumor cells. No patients have had metastases or local recurrence. Histologic, immunohistochemical, and clinical data from 71 cases of PMT, including the 11 cases in this report, confirm the benign behavior of these lesions. The etiology of these lesions is unclear, including the absence of surgical or other trauma in all of the children.

Adolescent↗
PubMed1995

Spindle cell hemangioendothelioma: a neoplasm associated with Maffucci's syndrome.

A case of a 21-year-old male with Maffucci's syndrome is presented in which the patient developed multiple cutaneous spindle cell hemangioendotheliomas (SHE). Recent reports suggest an association between spindle cell hemangioendotheliomas (SHE) and Maffucci's syndrome. Our case supports the interpretation that SHE is associated with Maffucci's syndrome.

Adult↗
PubMed1994

Aganglionosis and related disorders.

Congenital aganglionosis or Hirschsprung's disease (HD) characteristically presents with involvement of the sigmoid colon and rectum. There is an associated increase in cholinergic and adrenergic innervation in the affected bowel wall. Diagnosis of HD in the neonatal period is readily achieved via submucosal rectal biopsy with recognition of the immaturity of ganglion cells within the first year of life, use of a standardized protocol, and supplemental acetylcholinesterase stain. Morbidity and mortality from HD occur caused by Hirschsprung's-associated enterocolitis (HAEC); the pathologist can alert the clinician to the presence of HAEC. The HD variant to be aware of is total colonic aganglionosis, which may lack hypertrophic nerves and increased cholinergic nerve endings and contain zonal areas of some ganglion cells. Pseudo HD includes intestinal neuronal dysplasia (IND), chronic idiopathic intestinal pseudo obstruction (CIIP), and chronic constipation in children. Intestinal neuronal dysplasia is characterized by hyperganglionosis, whereas CIIP and chronic constipation in children share a common, newly described myopathic pathology. In this review investigation into peptidergic (VIPergic) innervation in pseudo HD and HD shows increased VIPergic immunostaining in CIIP, chronic constipation, and the ganglionic portion of HD; however, the VIPergic pattern is not diagnostically selective. Until the advent of new molecular biological techniques, histopathology remains the diagnostic gold standard in HD.

Child↗
PubMed1994

Characterization of somatostatin receptors on human neuroblastoma tumors.

Neuroblastoma is the most common extracranial solid tumor of children. Neuroblastoma tumors derive from the neural crest and synthesize neurotransmitters including the neuropeptide somatostatin. This study was designed to characterize somatostatin receptors both in primary neuroblastoma tumors and in two neuroblastoma cell lines, SKNSH and IMR32. Somatostatin receptors were identified in 6 of 7 Stage I and II compared to 7 of 19 Stage III and IV tumors. Down-regulation of somatostatin receptor binding was observed in five tumors during disease progression. A lack of high affinity binding of somatostatin was identified as a poor prognostic indicator; negative binding correlated with advanced disease and death. Somatostatin receptor binding was observed in the IMR32 cell line, but not in the SKNSH cell line. IMR32 cells demonstrated a single class of high affinity binding sites for both somatostatin and a synthetic analogue, octreotide (Kd 0.16 +/- 0.05 nM and 0.89 +/- 0.23 nM, respectively). Somatostatin and octreotide inhibited both vasoactive intestinal peptide-mediated and forskolin-mediated cyclic AMP accumulation in IMR32 cells. Somatostatin and octreotide inhibition of signal transduction was attenuated by pretreatment of the cells with pertussis toxin. Octreotide inhibited proliferation of IMR32 cells by 70% in a 6-day culture. In contrast, octreotide did not exhibit high affinity binding in SKNSH cells and had no effect on cyclic AMP accumulation or on proliferation in SKNSH cells. Together, these data indicate that octreotide interacts with high affinity somatostatin receptors to modulate signal transduction and regulate proliferation in neuroblastoma cell lines. These data also suggest that somatostatin receptor expression may be an independent prognostic factor in primary neuroblastoma tumors.

Binding, Competitive↗
PubMed1993

Evaluation of celiac disease biopsies for adenovirus 12 DNA using a multiplex polymerase chain reaction.

It has been postulated that celiac disease (CD) is initiated by adenovirus 12 infection (1). To test this hypothesis, we devised a PCR-based strategy to simultaneously screen for adenovirus 12 (Ad12), cytomegalovirus (CMV), and herpes simplex viruses (HSV) 1 and 2 in formalin-fixed paraffin-embedded small bowel biopsies from adult and childhood CD patients. Control groups consisted of small bowel biopsies from normal adults and children, adults with active peptic duodenitis, and children with active duodenitis. Ad12 DNA was found in two of 19 adult CD biopsies (two of 14 patients), while CMV and HSV DNA was found in one of the 19 adult CD biopsies. Ad12 and CMV DNA was not present in 19 child CD biopsies, while HSV DNA was found in two of these same biopsies. CMV and HSV DNA were not found in any of the control group patients. Ad12, CMV, and HSV DNA were not identified in significant numbers in any patient group. These findings argue against the presence of persistent adenovirus infection in CD patients but do not preclude remote Ad12 infection prior to the onset of CD. Similarly, the absence of CMV and HSV DNA in CD, active peptic disease in adults, and active duodenitis in children suggests that neither virus is involved in the persistence of these inflammatory conditions.

Adenoviruses, Human↗
PubMed1992

Neuroblastoma. Correlation of neuropeptide expression in tumor tissue with other prognostic factors.

BACKGROUND: The neuropeptide contents in neuroblastomas were quantified by radioimmunoassay (RIA) to assess their possible biologic significance. METHODS: Neuroblastoma tumor tissue was obtained from the primary tumor site before therapy in 16 patients with newly diagnosed neuroblastoma and in 7 patients with central nervous system medulloblastomas or gliomas. RESULTS: The tumor tissue was assayed for vasoactive intestinal peptide (VIP), somatostatin (SRIF), substance P, and neurotensin by both immunostaining and RIA techniques. Increased VIP levels of 1.2 pg/micrograms DNA or more correlated significantly with cellular differentiation (P = 0.003) and favorable disease stage (P = 0.002) in neuroblastomas. Increased SRIF contents (greater than 1.3 pg/micrograms DNA) correlated with differentiation of the tumor (P = 0.002). Increased VIP and SRIF content did not correlate with N-myc oncogene expression or ras oncogene protein immunostaining. No VIP was detectable in brain tumors, and other neuropeptides were variable in content. CONCLUSIONS: RIA of VIP and SRIF levels in primary tumor tissue may offer an independent objective assay of biologic behavior in neuroblastoma biopsy specimens.

Adolescent↗
PubMed1992

Vasoactive intestinal peptide: autocrine growth factor in neuroblastoma.

Neuroblastoma is the most common solid tumor of children less than 5 years of age; yet the biology of this tumor is poorly understood. Neuroblastoma tumors are derived from neural crest precursors; they synthesize both adrenergic and peptidergic neurotransmitters. This study determined VIP receptor expression in primary neuroblastoma tumors prior to chemotherapy. The VIP receptor was expressed in 12 of 15 neuroblastoma tumors as determined by direct binding studies (KD = 1.3-12.4 nM) and VIP-mediated stimulation of adenylate cyclase. The VIP stimulation index for adenylate cyclase in the primary tumor was inversely correlated with the VIP content of the tumor, suggesting that VIP regulates its own receptor expression. Similar observations were made in vitro by comparison of two human neuroblastoma cell lines, IMR32 and SKNSH. Both cell lines were demonstrated to express specific, high affinity VIP receptors (KD = 4 nM and 2.5 nM for IMR32 and SKNSH, respectively). IMR32 cells contained very low levels of VIP (0.6 pg VIP/10(6) cells). Exogenous VIP stimulated adenylate cyclase 22-fold over basal activity and VIP inhibited proliferation of IMR32 cells by 49% in 6-day cultures. On the other hand, SKNSH cells synthesized high levels of VIP (6.3 pg/10(6) cells), metabolized VIP rapidly and demonstrated a low level of VIP-mediated stimulation of adenylate cyclase; their proliferation rate was minimally inhibited by exogenous VIP. These observations help validate the hypothesis that VIP serves as an autocrine growth factor in neuroblastoma.

Adenylyl Cyclases↗