Biomedical subjects

P Thorner

Publications and source records attributed to P Thorner.

At least 55 records · Page 3Linked to original sources

PubMed1993

Localized scleroderma progressing to systemic disease. Case report and review of the literature.

We describe a 15-year-old girl with biopsy-proven morphea who developed progression to systemic disease 2 years after initial presentation. In contrast to other reported patients with localized scleroderma, some of whom have had mild, nonprogressive systemic involvement, this patient developed severe, debilitating disease, with skin tightness, sclerodactyly, esophageal involvement, restrictive pulmonary disease, and myopathy. From the time of her initial evaluation, the patient was positive for antinuclear antibodies (ANA), which were shown to be primarily directed against the Ku antigens. This observation suggests that ANA may be a prognostic indicator for progression to systemic disease.

Antibodies, Antinuclear↗

PubMed1993

Variant translocations of chromosome 22 in Ewing's sarcoma.

Relatively few variant translocations have been reported in primary Ewing's sarcomas (ES). We report two new variant translocations, both of which involve chromosomal rearrangements of 22q12. Cytogenetic studies of tumor cells from a 12-year-old girl revealed a variant translocation, t(7;22)(p22;q12), the second example reported of a simple variant of the 22q12 reciprocal translocation in this type of sarcoma. The identity of this rearrangement was confirmed by in situ hybridization. In addition, a complex translocation was identified in a dysmorphic 15-year-old girl, t(4;11;22)(q21;q24;q12). No previous cases of variant translocations in ES have involved band 7p22 or 4q21, and there are no previous reports of an association between congenital abnormalities and unusual karyotype abnormalities in ES. Both variant translocations conserve the junction on the der (22), providing additional cytogenetic evidence that the sequences on chromosome 22 are critical.

Child↗

PubMed1993

Sonographic appearance of Sertoli cell tumour: with pathologic correlation.

Sertoli cell tumor is a rare tumor of the testis, with a good prognosis following orchiectomy in the pediatric patient. Sonography of such a tumor in a 5-year-old boy revealed diffuse inhomogeneous increase in echogenicity in an enlarged left testicle. The increased echogenicity of the testicle reflected the dense collagenous matrix of the lesion.

Child, Preschool↗

PubMed1993

Malignant benign neonatal sacrococcygeal teratoma.

Thirty-six patients with benign neonatal sacrococcygeal teratoma (SCT) were treated in our medical center from 1972 to 1990. Mean gestational age was 38.6 +/- 3.3 weeks with a mean birth weight of 3,484.0 +/- 938.5 g. Twenty-nine patients (89%) were females. The majority of the tumors (75%) contained cystic components and 96% were Altman classification I and II. The initial surgical removal of the SCT (including the coccyx) was carried out during the first 7 days of life. Six patients (22%) developed recurrence of the tumor. Three were benign and reappeared locally after 12 +/- 3 months and were reexcised. The mean serum alpha-fetoprotein level in this group was 13 +/- 1 g/L. The malignant recurrence (all originally reported as being mature benign SCT) appeared at 20.3 +/- 1.5 months and had markedly elevated serum alpha-fetoprotein levels (7,320 +/- 4,630 micrograms/L). All the patients in this group had multimodal therapy including complete excision of the recurrent tumor. We conclude that SCT, although histologically benign, has an alarming potential to recur either as a benign or malignant tumor during the first 2 years of life. Close follow-up for at least 3 years (frequent examination, serum alpha-fetoprotein, and diagnostic imaging) is recommended for all patients who had undergone excision of SCT in the newborn period.

Combined Modality Therapy↗

PubMed1993

Fetal tendon healing: development of an experimental model.

An experimental model was developed to study the process of fetal tendon healing. The flexor digitorum profundus tendons of the right hindlimb of 14 fetal lambs were partially lacerated at 100 days' gestation (term 145 days) and then studied macroscopically and histologically at several postinjury intervals (2, 4, 7, 14, 28, 42, and 56 days); two lambs were studied at each interval. A similar procedure was done in 14 adult sheep, who served as a control group. The fetal lambs showed no subcutaneous scarring, the digital sheath and tendon healed 2 weeks after injury, and a smooth, gliding surface was reconstituted. Collagen fibers were randomly arranged at 1 week but became organized along the tendon axis by 2 weeks. No adhesions, ruptures, or triggering was noted in the healing fetal tendons. Normal morphology was restored by 6 weeks. In the adult, dense subcutaneous scarring was noted, the digital sheath healed by 4 weeks and the tendon gap by 6 weeks, but a smooth gliding surface was not restored. Collagen fibers were randomly arranged at 2 weeks and became organized along the tendon axis by 4 weeks after injury. There were no dense adhesions or ruptures, but 25 percent of the tendons showed triggering.

Animals↗

PubMed1993

Detection of MYCN gene amplification and deletions of chromosome 1p in neuroblastoma by in situ hybridization using routine histologic sections.

BACKGROUND: Amplification of the MYCN oncogene and partial deletion of chromosome 1p are genetic changes frequently seen in neuroblastoma that are indicators of poor prognosis. The identification techniques usually used--Southern blotting for MYCN gene amplification, and karyotypic analysis of viable tumor cells for large 1p deletions--are time-consuming and suited for specialized laboratories. EXPERIMENTAL DESIGN: We have developed an immunofluorescence in situ hybridization assay suitable for detection of MYCN amplification and 1p deletion in formalin-fixed, paraffin-embedded tissue sections. The technique is rapid, does not involve the use of radioactivity, and can be carried out in laboratories already familiar with conventional in situ hybridization and immunohistochemical detection methods. RESULTS: MYCN gene amplification appeared as multiple signals per nucleus, corresponding to double minute chromosomes. Deletion of 1p was detected by loss of one of the normal signals present within the nucleus of a neuroblastoma cell line. Use of different fluorophores enabled the simultaneous detection of MYCN gene amplification and 1p deletion at the individual cell level. Detection was found to be enhanced by RNase and pepsin treatment of tissue sections before hybridization and by a novel microwave denaturation method. CONCLUSIONS: Application of this methodology to formalin-fixed samples of neuroblastoma will permit comprehensive retrospective studies of these two genetic markers using archived tumors. In situ hybridization surveys will have widespread applications for studying known genetic aberrations in individual cells of a variety of solid tumors and for determining interrelationships and clinical significance in relation to tumor progression and patient outcome.

Chromosomes, Human, Pair 1↗

PubMed1992

Sonography of multinodular thyroid gland in children and adolescents.

Multinodular disease of the thyroid gland is uncommon in children and adolescents, and has received little attention in the recent literature. This article reviews the clinical, sonographic, and pathologic findings in 16 children with multinodular disease of the thyroid gland, and draws attention to the high incidence of other associated clinical findings. This condition was associated with a triad including renal and digital anomalies in three patients, with McCune-Albright syndrome in two patients, with Hashimoto's thyroiditis in three patients, and with thyroid carcinoma in four patients. Three of five patients with a history of previous radiation therapy had thyroid carcinoma. Sonography is a proven valuable imaging modality for the study of thyroid disease in children and has contributed to our understanding of multinodular disease of the thyroid gland in this age group.

Adolescent↗

PubMed1992

MRI of fibromatosis: with pathologic correlation.

Fibromatosis refers to group of benign but sometimes locally aggressive proliferative lesions of myofibroblasts. These are characterized by infiltrative growth, and hence may mimic a malignant lesion. These lesions reveal a low signal intensity on T1-weighted pulse sequences, but may show low or high signal intensity on the T2-weighted sequences. Histologic correlation reveals that the lesion showing low signal intensity on T2-weighted sequences has a larger collagenous component, and reduced cellularity compared with the lesion showing high signal intensity on T2-weighted sequences.

Child↗

PubMed1992

A 20-year review of pediatric pancreatic tumors.

Pancreatic tumors are rare surgical problems in infants and children. A 20-year audit (1971 to 1991) of this institution showed six patients ranging in age from 3 weeks to 16 years who were operated on for pancreatic neoplasms. Five of these tumors were malignant, bringing the reported experience to 71 cases. This series of malignancies included three solid cystic tumors, one insulin-secreting tumor, and one pancreatoblastoma. The clinical presentations varied: three had abdominal pain, one developed hypoglycemia, and one had an abdominal mass with jaundice. In five of the six patients pancreatic pathology was suspected preoperatively. All were treated primarily with pancreatic resection including one pancreatoduodenectomy. No radiotherapy or chemotherapy was used. The perioperative mortality was 0% with a morbidity of 50%. The long-term results are encouraging, with all patients alive after a mean follow-up of 7.8 years. These data suggest that aggressive surgical therapy is warranted in the management of pediatric pancreatic tumors.

Adenoma, Islet Cell↗

PubMed1992

Coordinate expression of Wilms' tumor genes correlates with Wilms' tumor phenotypes.

The cloning and molecular characterization of two putative tumor genes, WT1 and WIT1, from the chromosome 11p13 region has provided a means of evaluating their role in the generation of Wilms' tumor heterogeneity. A series of 29 tumors were analyzed for WT1 and WIT1 expression by Northern blot or RNase protection analyses, and results were compared with tumor histopathology. Tumors were scored for the percentage of mesenchymal and epithelial derived tissue components. Homotypic tumors comprised blastema, tubular epithelium, and a fibroblast-like mesenchyme. In addition to these tissue components, the group of tumors designated as heterotypic also contained ectopic cell phenotypes such as muscle and squamous epithelium. The analyses suggest that heterotypic differentiation patterns occur when WT1 and WIT1 expression is low relative to normal fetal kidney. In situ hybridization using antisense RNA probes showed that WT1 and WIT1 were concordantly expressed in normal fetal kidney and in the blastema of tumors. The ratio of WT1:WIT1 expression remained relatively constant in homotypic tumors but deviated significantly in heterotypic tumors. These results suggest that expression patterns of the WT1 and WIT1 genes can be closely correlated to Wilms' tumor histopathology.

Blotting, Northern↗

PubMed1992

Differential kinetics of engraftment and induction of CD10 on human pre-B leukemia cell lines in immune deficient scid mice.

The sensitivity of the scid mouse model was assessed by comparing the growth of two pre-B acute lymphoblastic leukemia (ALL) cell lines, A1 and G2, established from patients at relapse. When cell numbers varying from 10(4) to 10(7) were injected intravenously into scid mice, advanced growth and dissemination of leukemia was observed at 10-12 weeks with the G2 cells. Bone marrow, spleen and thymus contained high levels of human leukemic cells and infiltration into lung, kidney, liver, and brain was observed. Two of three mice grafted with only 100 cells showed high levels of infiltration at 15 weeks, suggesting that 100 G2 cells was near the limiting cell number that could produce disseminated leukemia. With the A1 line, a minimum of 10(5) cells was needed to obtain dissemination to liver, lung, brain, and kidney; a low level of spleen infiltration occurred and thymus invasion was not observed. In vitro, both lines showed a density dependent growth in clonogenic assays but the cloning efficiency of the A1 line was 10-fold higher than for G2 cells. These results indicate that G2 and A1 lines have a dissimilar aggressiveness in vivo which does not correlate with clonogenic assay in vitro. Neither G2 nor A1 lines, growing in vitro, expressed CD10/CALLA on their surface, despite low levels of antigen on the freshly obtained relapse samples. Although A1 cells remained CD10-negative in the scid mice, G2 cells showed detectable levels of CD10, particularly on those cells found in the thymus. Several subclones of the G2 line were derived from isolated colonies in vitro; they were found to be CD10- in vitro, but to become CD10+ when proliferating into scid mouse thymus, suggesting the induction of CD10 by the murine microenvironment.

Animals↗

PubMed1991

Bone marrow from children in relapse with pre-B acute lymphoblastic leukemia proliferates and disseminates rapidly in scid mice.

Bone marrow samples from patients with pre-B acute lymphoblastic leukemia (pre-B ALL), either at diagnosis or at relapse, were transplanted into scid mice to determine whether these freshly obtained leukemic cells could proliferate in vivo and whether there were any differences in their in vivo growth characteristics. Cells from three patients who relapsed within 13 months of diagnosis proliferated rapidly in the murine bone marrow, spleen, and thymus, invaded peripheral organs, and resulted in morbidity and mortality of the animals within 4 to 16 weeks. Cells from two patients who relapsed 3.5 years after diagnosis grew much slower than the early relapse samples, taking up to 30 weeks to infiltrate the bone marrow of recipient mice. In contrast, leukemic cells were absent or were detected at low numbers in scid mice transplanted with cells obtained at diagnosis from three patients who have not yet relapsed. These results show an increased ability of leukemic cells from patients with aggressive lymphoblastic leukemia of poor prognosis to proliferate in scid mice.

Adolescent↗

PubMed1991

Ewing's sarcoma: metastatic tumor to the jaw.

Metastatic tumors to the jaw are a rare occurrence. The incidence of metastatic Ewing's sarcoma to the jaw has been reported to be less than 2% of all cases of Ewing's sarcoma. Early detection of such lesions is difficult because the signs and symptoms do not appear until the lesion has progressed considerably. The treatment options are therefore limited to palliative care of the patient rather than cure. This article reports a case of Ewing's sarcoma that had metastasized to the mandible and reviews the literature.

Carboplatin↗

PubMed1991

Reduction in tumor burden allowing partial nephrectomy following preoperative chemotherapy in biopsy proved Wilms tumor.

During the last 6 years a treatment protocol of radiographic staging along with percutaneous biopsy to establish a histological diagnosis has been used in 37 patients with Wilms tumor. Combination chemotherapy was given for 4 to 6 weeks before definitive surgical resection. In 9 patients tumor shrinkage was sufficient to permit preservation of a portion of the affected kidney(s). In stage V disease partial nephrectomy was accomplished in 5 patients. In 4 additional patients with unilateral disease downstaging also allowed partial nephrectomy. The radiological and histological changes that allowed this limited surgery are analyzed and compared.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1991

Adenosine deaminase and thymocyte maturation.

The congenital absence of adenosine deaminase in humans results in severe combined immunodeficiency. To clarify the process whereby thymocytes are destroyed in the absence of adenosine deaminase activity, we induced a parallel condition in mice through the injection of an inhibitor of adenosine deaminase, deoxycoformycin. We have observed that deoxycoformycin, in addition to maintaining high levels of dATP in thymocytes, blocks the progression of thymocyte differentiation at two points. As a result of the first block, the cortex is depleted of immature cortical thymocytes while CD4+CD8+ thymocytes with functionally rearranged T-cell receptors survive. As a result of the second block, the CD4+CD8+ thymocytes are prevented from further differentiation to mature CD4+CD8- or CD4-CD8+ T lymphocytes and accumulate at the corticomedullar junction and in the medulla. These observations suggest that the maintenance of dNTP pools by adenosine deaminase is critical to at least two stages of thymocyte differentiation.

Adenosine Deaminase↗

PubMed1991

Spontaneous pneumothorax in cystic adenomatoid malformation. Unusual clinical and histologic features.

Pneumothorax is a rare presentation of congenital cystic adenomatoid malformation (CCAM) in the newborn period and is presumed to be due to resuscitative measures. A previously well three-week-old baby presented with spontaneous tension pneumothorax due to CCAM. In the lung resection specimen, a malformation was seen, which in addition to the histologic changes of CCAM, showed diffuse vascular proliferation in the interstitium and lining of air space by type 2 pneumocytes. We propose that this is a new variant of CCAM rather than one of the classic three types. The unusual clinical manifestation may be related to the unusual histologic features.

Cystic Adenomatoid Malformation of Lung, Congenita↗

PubMed1991

Arteriopathy and coarctation of the abdominal aorta in children with mucopolysaccharidosis: imaging findings.

Eight children with mucopolysaccharidosis I (MPS I), representing 33% of all children with MPS I seen at our institution during an 18-year period, developed hypertension. Five of these hypertensive children also exhibited symptoms of aortic coarctation. The radiographic evaluation of four of these children with MPS I (three with Hurler syndrome, MPS I H, and one with Scheie disease, MPS I S) and arteriopathy affecting the thoracic aorta, abdominal aorta, and visceral and renal arteries is presented. Hypertension developed in all four children before they were 4 years old; three had differences between upper- and lower-extremity blood pressures. Irregular narrowing of the abdominal aorta with either multiple minor asymmetric wall lesions (n = 2) or abrupt concentric narrowing (n = 2) was present in all children as shown by aortography (n = 3), sonography (n = 3), MR imaging (n = 2), and/or autopsy (n = 1). A variety of other vessels also were involved, including the ascending aorta (n = 1) and vertebral (n = 1), axillary (n = 1), intercostal (n = 2), lumbar (n = 2), mesenteric (n = 3), renal (n = 2), and iliac arteries (n = 3). Autopsy in one child demonstrated thickened heart valves, narrowing of the coronary arteries, and irregularity of the aorta due to deposition of mucopolysaccharide material within the intima. Our series demonstrates various facets of the arteriopathy of MPS I as shown by sonography, MR imaging, and angiography.

Angiography↗

PubMed1991

Renal disease in carrier female dogs with X-linked hereditary nephritis. Implications for female patients with this disease.

Male dogs with X-linked hereditary nephritis (HN) serve as a model for studying male patients with this disease. In the present study, carrier female dogs were found to resemble female patients in showing a broad range of renal dysfunction. Of 37 carrier female dogs studied, all were healthy up to 5 years of age; however, all had proteinuria develop at 2 to 3 months, and focal segmental glomerulosclerosis (FSGS) was detected after 7 months. After 5 years, 4 of 13 dogs remained healthy and showed mild FSGS on renal biopsy; 4 had mild renal dysfunction develop and their kidneys showed extensive FSGS; 5 died prematurely of renal failure with end-stage kidneys. By immunofluorescence, using antibody to the NC1 domain of collagen type IV, segmental staining of glomerular basement membranes (GBM) was seen in all dogs before 3 to 4 years, and lesions of FSGS were negative. Thereafter, a transition to global staining of GBM was noted and lesions of FSGS became positive. Lens capsule and basement membranes in lung and choroid plexus showed discontinuous staining in two young carrier female dogs and continuous staining in one older carrier female dog. By electron microscopy, multilaminar splitting of some GBM was seen up to 4 years, and thereafter, splitting took on a compressed appearance, with the layers becoming apposed though still detectable. The authors conclude that: 1) carrier female dogs with X-linked HN are mosaics for an abnormality in the NC1 domain of GBM and other basement membranes; 2) FSGS develops in all carrier female dogs in glomerular capillary loops that possess an abnormal NC1 domain, and progresses to a variable extent in different dogs; and 3) the abnormality of NC1 in GBM of carrier female dogs appears to diminish with age, but this does not prevent progression of renal disease. Similar conclusions may apply to females with X-linked HN.

Animals↗