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D M Parham

Publications and source records attributed to D M Parham.

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

Implications of a common polymorphism in intron 12 of the dystrophin gene for deletion detection by multiplex PCR.

The multiplex polymerase chain reaction (PCR) is a reliable and efficient method for detecting dystrophin gene deletions in about 65% of patients with Duchenne or Becker muscular dystrophy (DMD or BMD). The 9-plex PCR assay, which simultaneously amplifies the muscle-specific promoter and exons 3, 6, 13, 43, 47, 50, 52 and 60, is one of the multiplex PCR assays used routinely to test for DMD and BMD deletions. In this study, we describe a previously unrecognized A to G base variation in intron 12 (nt -110 from exon 13) of the dystrophin gene. This variant, located within the annealing site of the exon 13 forward primer, prevented amplification of exon 13 in the 9-plex PCR assay. Present in 56% (25 of 45) of normal Caucasian alleles and 23% (3 of 13) of normal black American alleles, it is likely encountered frequently during dystrophin deletion analysis by multiplex PCR, and may complicate test result interpretation. Therefore, we suggest two modifications for the multiplex PCR detection of dystrophin gene deletion.

Alleles↗
PubMed1998

A simple method of tumour culture.

We describe a simple explant primary cell culture system which maintains the normal tumour stroma relationship. This technique utilises conventional cell culture methods combined with the skills found in the histopathological laboratory. This produces sections of tumour visible by light microscopy. Using this method we were able to maintain for up to 7 days good morphological preservation and demonstrated continued proliferation. This technique produces histological sections of tumour following in vitro culture that can be utilised for other molecular studies, e.g. immunohistochemistry and in situ PCR. This method should prove invaluable to pathologists enabling direct visualisation and localisation of molecular events involved in tumour growth.

Adenocarcinoma↗
PubMed1998

Methylation alterations of the MyoD1 upstream region are predictive of subclassification of human rhabdomyosarcomas.

MyoD1 expression is a distinguishing characteristic of rhabdomyosarcoma. In this study, distinct methylation alterations were identified in the 5' flanking region of the MyoD1 gene from the two major subtypes, ie, alveolar and embryonal rhabdomyosarcoma. The MyoD1 methylation patterns of 26 rhabdomyosarcomas were compared with that of normal skeletal muscle and nonmuscle specimens by Southern blot analysis using methylation-sensitive restriction enzymes HhaI and HpaII. A 5-kb region immediately upstream of the MyoD1 coding sequence was found to be methylated in adult muscle and all nonmuscle tissues tested. The MyoD1 upstream region was unmethylated in the majority of the alveolar rhabdomyosarcomas (13 of 15, 87%) examined in this study. In contrast, 10 of 11 (91%) embryonal rhabdomyosarcomas showed a methylation pattern that was also observed in fetal muscle cells, in which the CpG sites in the MyoD1 upstream region were partially methylated. Our data suggest that the methylation status of the MyoD1 upstream CpG sites may be related to rhabdomyosarcoma tumorigenesis and may have valuable implications for its differential diagnosis.

Adolescent↗
PubMed1997

Is primitive neuroectodermal tumor of the kidney a distinct entity?

BACKGROUND: Primitive neuroectodermal tumors (PNETs) constitute a family of neoplasms of presumed neuroectodermal origin, most often presenting as bone or soft tissue masses in the trunk or axial skeleton in adolescents and young adults. As a soft tissue neoplasm, PNET arising in the kidney has not been well described, with only three cases previously reported. METHODS: Four patients with PNET of the kidney were diagnosed and treated at St. Jude Children's Research Hospital. The authors reviewed the clinical, radiologic, and pathologic features and outcomes of these cases and of those previously described. RESULTS: The authors' patients were age 4-20 years. They presented with unilateral renal masses and metastatic disease in the lymph nodes (three patients), lungs (three patients), bone (two patients), liver (one patient), and bone marrow (one patient). Treatment included surgery, radiotherapy, and multiagent chemotherapy. Three of the patients died of progressive disease within 14 months of diagnosis. Features and outcomes were similar to those of the three previously reported cases. CONCLUSIONS: PNET of the kidney appears to be a distinct entity. Although rare, it must be included in the differential diagnosis of renal tumors in children and young adults. Patients usually present with advanced disease and show poor response to combined-modality therapy.

Adolescent↗
PubMed1997

Undifferentiated rhabdomyosarcoma with lymphoid phenotype expression.

Poorly differentiated rhabdomyosarcomas are traditionally distinguished from lymphomas by their absence of lymphoid markers such as immunoglobulin or CD20 expression. We have encountered three alveolar rhabdomyosarcomas that were initially diagnosed as lymphoid neoplasms because of the expression of a lymphocytic phenotype in morphologically undifferentiated tumor cells. Subsequent cytogenetic analysis revealed a t(2; 13) in two cases. All cases recurred in the chest wall and showed positivity for muscle markers, such as muscle-specific actin, myoglobin, MyoD1, and/or desmin on subsequent immunohistochemistry. The findings in these three cases lead us to conclude that the presence of a lymphoid phenotype does not absolutely exclude the diagnosis of rhabdomyosarcoma.

Adolescent↗
PubMed1997

The role of esophagoscopy in diagnosis and management of esophagitis in children with cancer.

Esophagitis is a common complication in patients treated for cancer; however, difficulty in determining its etiology on the basis of noninvasive clinical information limits the implementation of specific therapies. We reviewed our experience with esophagoscopy and biopsy as an aid in the diagnosis and management of esophagitis in children with cancer. Of eleven episodes of esophagitis evaluated by esophagoscopy with biopsy, four (36%) had an infectious etiology (two with Candida, one with Herpes simplex virus, and one with viridans streptococci). The absolute neutrophil count, presence of oropharyngeal colonization, and appearance of the esophagus at esophagoscopy were not predictive of the etiology of esophagitis. Esophagoscopy with biopsy affected the management of 4 (36%) patients. We believe this procedure to be a valuable aid in managing esophagitis in children with cancer by providing objective data not otherwise available to the clinician.

Adolescent↗
PubMed1997

MR imaging differentiation of benign and malignant peripheral nerve sheath tumors: use of the target sign.

BACKGROUND: T2-weighted MR imaging of soft tissue tumors of neural origin may show round lesions with a central hypointensity and a hyperintense rim resembling a target. We define the "target sign" as a mass consisting of a solitary target, or a multicompartmental mass in which the largest component consists of multiple targets. OBJECTIVE: The objective of this study was to determine whether the target sign can differentiate benign neurofibromas and their malignant counterparts, malignant peripheral nerve sheath tumors. Materials and methods. Preoperative T2-weighted MR images of 23 neurofibromas or malignant peripheral nerve sheath tumors were retrospectively reviewed in 16 patients, aged 3 weeks to 20 years (median 15 years), without knowledge of the pathologic diagnosis. The presence or absence of a target sign was noted. RESULTS: The target sign was seen in all 12 neurofibromas and 1 of the 11 malignant peripheral nerve sheath tumors. Statistical analysis showed good differentiation of benign and malignant tumors using this sign (chi = 0.91). CONCLUSION: The target sign on T2-weighted MR imaging is helpful in differentiating neurofibromas from malignant peripheral nerve sheath tumors.

Adolescent↗
PubMed1997

Angiosarcomas of the breast developing post radiotherapy.

AIMS: This paper describes two contrasting cases of post-radiotherapy angiosarcomas of the breast. They illustrate the spectrum of malignant vascular tumours that may occur in the breast. These tumours are extremely rare and knowledge of their natural history is limited. The prognosis suggested by the few published cases of poorly or moderately differentiated angiosarcomas suggest a poor prognosis often with a fatal outcome. METHODS AND RESULTS: This was confirmed by our first case a poorly differentiated angiosarcoma, occurring 10 years after radiotherapy for breast carcinoma with death occurring from metastatic angiosarcoma 6 months later. Our second, more recently diagnosed case, was a well-differentiated angiosarcoma, occurring 5 years post radiotherapy for breast cancer. She remains well 12 months after the diagnosis of sarcoma but her long-term outlook is more problematic to predict. Only five previous cases of well-differentiated post-radiotherapy angiosarcoma of the breast have been reported with limited follow-up (average 2 years). CONCLUSIONS: Communication with the authors of four of the papers since their publication has provided valuable additional information and indicates a potentially good outlook for this woman in the longer term. A second cellular component was also found in these malignant vascular tumours. These spindle cells distinct from the malignant endothelial cells have not to our knowledge been described previously and their possible nature is discussed.

Aged↗
PubMed1996

Methods to detect P-glycoprotein-associated multidrug resistance in patients' tumors: consensus recommendations.

Multidrug resistance (MDR), especially that associated with overexpression of MDR1 and its product, P-glycoprotein (Pgp), is thought to play a role in the outcome of therapy for some human tumors; however, a consensus conclusion has been difficult to reach, owing to the variable results published by different laboratories. Many factors appear to influence the detection of Pgp in clinical specimens, including its low and heterogeneous expression; conflicting definitions of detection end points; differences in methods of sample preparation, fixation, and analysis; use of immunological reagents with variable Pgp specificity and avidity and with different recognition epitopes; use of secondary reagents and chromogens; and differences in clinical end points. Also, mechanisms other than Pgp overexpression may contribute to clinical MDR. The combined effect of these factors is clearly important, especially among tumors with low expression of Pgp. Thus, a workshop was organized in Memphis, Tennessee, to promote the standardization of approaches to MDR1 and Pgp detection in clinical specimens. The 15 North American and European institutions that agreed to participate conducted three preworkshop trials with well-characterized MDR myeloma and carcinoma cell lines that expressed increasing amounts of Pgp. The intent was to establish standard materials and methods for a fourth trial, assays of Pgp and MDR1 in clinical specimens. The general conclusions emerging from these efforts led to a number of recommendations for future studies: (a) although detection of Pgp and MDR1 is at present likely to be more reliable in leukemias and lymphomas than in solid tumors, accurate measurement of low levels of Pgp expression under most conditions remains an elusive goal; (b) tissue-specific controls, antibody controls, and standardized MDR cell lines are essential for calibrating any detection method and for subsequent analyses of clinical samples; (c) use of two or more vendor-standardized anti-Pgp antibody reagents that recognize different epitopes improves the reliability of immunological detection of Pgp; (d) sample fixation and antigen preservation must be carefully controlled; (e) multiparameter analysis is useful in clinical assays of MDR1/Pgp expression; (f) immunostaining data are best reported as staining intensity and the percentage of positive cells; and (g) arbitrary minimal cutoff points for analysis compromise the reliability of conclusions. The recommendations made by workshop participants should enhance the quality of research on the role of Pgp in clinical MDR development and provide a paradigm for investigations of other drug resistance-associated proteins.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Alveolar soft part sarcoma in children and adolescents: clinical features and outcome of 11 patients.

The clinical features and response to therapy of pediatric alveolar soft part sarcoma, a rare soft tissue sarcoma of uncertain histogenesis, have not been previously described in detail in the literature. We retrospectively reviewed the clinical characteristics of all patients with alveolar soft part sarcoma who were seen at our institution over a 32-year period. We found 11 patients with the diagnosis of alveolar soft part sarcoma. Their ages ranged from 2.8-16 years (median 9.8). Staging was determined using the Intergroup Rhabdomyosarcoma Study clinical grouping system and the UICC TNM system. Accordingly, there were six patients with grossly resected tumors (clinical groups I and II) and five with unresected or metastatic disease (clinical groups III and IV). Children with resected disease were more likely to have smaller noninvasive tumors. The main feature predictive of survival was tumor resectability, since chemotherapy in various combinations failed to produce significant tumor responses. Nine patients are disease-free with a median follow-up of 11.9 years. Surgical resection remains the mainstay of therapy for pediatric alveolar soft part sarcoma. Since active chemotherapy agents have not been identified, patients with unresected or metastatic disease may benefit from experimental agents. The survival rate of this cohort is superior to that seen in adults.

Adolescent↗
PubMed1996

Outcome in 43 children presenting with metastatic Ewing sarcoma: the St. Jude Children's Research Hospital experience, 1962 to 1992.

The purpose of this work was to review the St. Jude Children's Research Hospital experience of patients presenting with metastatic Ewing sarcoma over a 30-year period. Forty-three of 212 cases of Ewing sarcoma presented with metastases at diagnosis. These patients were analyzed to determine whether primary tumor site or size, metastatic site(s), or advances in therapy have had a positive impact on survival. The overall survival for our 43 patients was 35% (95% confidence intervals, 20% to 50%). Comparing patients treated prior to 1979 with those treated after 1979, the overall survival was significantly different (P = 0.0002). Comparing overall survival between pelvic and non-pelvic primaries (P = 0.24), among metastatic sites (P = 0.83), and between tumors measuring > 8 cm in diameter to tumors measuring < 8 cm in diameter (P = 0.12), no significant differences were observed. Approximately one-third of patients presenting with metastatic Ewing sarcoma may achieve long-term survival. Children with metastatic Ewing sarcoma may benefit from clinical trials which intensify the doses of doxorubicin, and the highly effective combination of ifosfamide/etoposide.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

Role of irradiation in management of synovial sarcoma: St. Jude Children's Research Hospital experience.

The role of irradiation in the management of synovial sarcoma (SS) in pediatric patients is evaluated. The review covers all children seen at St. Jude Children's Research Hospital between May 1969 and December 1992 with the diagnosis of soft tissue sarcoma, of the 37 patients with the subtype SS, 16 received irradiation for the management of primary site disease. There were four IRS Group I, six Group II, four Group III, and two Group IV patients receiving irradiation. Tumor grade included seven Grade II, and nine Grade III lesions. TMN staging identified eight T1 and eight T2 lesions. Follow-up has ranged from 14 to 117 months (med = 33 months). All IRS Group I patients had documented local control. Five of six IRS Group II and 4/4 Group III patients have had documented local control at last follow-up. IRS Group IV patients had either local control tumor stabilization (n=1) or evidence of tumor regression (n=1) at autopsy. Complications following irradiation include wound dehiscence (n=1), surgery to revise a painful scar (n=1) extremity length discrepancy (n=2), and femoral head avascular necrosis (n=1). At last follow-up, 10 of 14 patients receiving curative intent irradiation remain alive. This review indicates questionable benefit to the addition of irradiation for patients with adequate surgical resection and having "good" tumor characteristics (Grade I, II; IRS Group I, TMN T1A,T1B. For lesions that have had incomplete resection or partial response to chemotherapy, there is evidence that irradiation may provide durable local control. The role of irradiation in those patients with IRS Group IV disease is at present confined to palliative roles until the time when more effective chemotherapy will mandate the decision to treat primary disease for curative measures.

Adolescent↗