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Biomedical subjects

Richard A Prayson

Publications and source records attributed to Richard A Prayson.

At least 19 recordsLinked to original sources
PubMed2006

Fibrin glue system for adjuvant brachytherapy of brain tumors with 188Re and 186Re-labeled microspheres.

Brain tumors such as glioblastoma reappear in their original location in almost 50% of cases. To prevent this recurrence, we developed a radiopharmaceutical system that consists of a gel applied immediately after surgical resection of a brain tumor to deliver local radiation booster doses. The gel, which strongly adheres to tissue in the treatment area, consists of fibrin glue containing the beta-emitters rhenium-188 and rhenium-186 in microsphere-bound form. Such microspheres can be prepared by short (2 h or less) neutron activation even in low neutron flux reactors, yielding a mixture of the two beta-emitters rhenium-188 (E(max)=2.1 MeV, half life=17 h) and rhenium-186 (E(max)=1.1 MeV, half life=90.6h). The dosimetry of this rhenium-188/rhenium-186 fibrin glue system was determined using gafchromic film measurements. The treatment efficacy of the radioactive fibrin glue was measured in a 9L-glioblastoma rat model. All animals receiving the non-radioactive fibrin glue died within 17+/-3 days, whereas 60% of the treated animals survived 36 days, the final length of the experiment. Control animals that were treated with the same amount of radioactive fibrin glue, but had not received a previous tumor cell injection, showed no toxic effects over one year. The beta-radiation emitting rhenium-188/rhenium-186-based gel thus provides an effective method of delivering high doses of local radiation to tumor tissue, particularly to wet areas where high adhesive strength and long-term radiation (with or without drug) delivery are needed.

Adhesiveness↗
PubMed2006

Role of MIB1 in predicting survival in patients with glioblastomas.

BACKGROUND: Histologic immunomarkers of cell cycle proteins have been utilized for prognosis in high-grade astrocytic tumors. One such marker, MIB1, an antibody immunoreactive throughout the cell cycle, is predictive of more aggressive disease and poorer prognosis in astrocytomas. An independent role of MIB1 analysis for survival prediction and clinical management within histologic grades has not been clearly proven. METHODS: This study retrospectively evaluated MIB1 reactivity in tissue samples from 116 patients with glioblastomas on initial medical presentation. Clinical variables considered included gender, age, Karnofsky Performance Scores (KPS), extent of surgical resection, adjuvant radiation and survival. RESULTS: Univariate and multivariate analyses were used to correlate these variables with MIB1 staining. MIB1 staining does not predict overall survival or response to adjuvant therapy as an independent risk factor. CONCLUSION: MIB1 labeling does not predict patient survival as an independent variable and does not predict response to additional therapies. Patient survival with glioblastoma was predicted by KPS, age, extent of resection and use of adjuvant radiotherapy.

Adult↗
PubMed2006

Thyroid transcription factor-1 staining is useful in identifying brain metastases of pulmonary origin.

Metastatic carcinomas of the brain are a common intracranial tumor and may be the first manifestation of the cancer in a patient. The primary site of these tumors is often difficult to determine based solely on histology. Thyroid transcription factor-1 (TTF-1) is a fairly specific immunohistochemical marker for primary lung and thyroid carcinomas. Recent studies have indicated that TTF-1 may be useful in identifying metastatic brain carcinomas arising from primary lung carcinomas. This study evaluates TTF-1 immunoreactivity in 101 metastatic brain carcinomas and 50 glioblastoma multiform. In patients with a known pulmonary primary, 59% of the metastases were positive for TTF-1. The one patient with a thyroid primary also had a metastasis positive for TTF-1. None of the metastatic lesions arising from other sites was positive for TTF-1. None of the 50 glioblastoma multiform was positive for TTF-1. This study indicates that TTF-1 may be useful in evaluating metastatic carcinomas of unknown primary and TTF-1 immunoreactivity may be indicative of a lung or thyroid primary.

Brain Neoplasms↗
PubMed2006

JC virus chromogenic in situ hybridization in brain biopsies from patients with and without PML.

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system caused by the JC polyoma virus. Electron microscopy and immunohistochemistry are the traditional methods of confirming the presence of the virus in brain biopsies from these patients. We studied the brain biopsies from 7 patients with PML and 6 patients without PML with chromogenic in situ hybridization (CISH) for the JC polyoma virus using a commercially available probe. The biopsies from the patients with the PML cases were proven to contain the JC polyoma virus by traditional and molecular methods. The CISH findings were compared with the known state of infection. All (7/7) of the biopsies from patients with PML were positive for the presence of polyoma virus by CISH, whereas the biopsies from patients without PML were uniformly negative. CISH seems to be a useful tool for the detection of the JC virus in brain biopsies from patients with PML, and is more accessible because a commercial probe is available.

Brain↗
PubMed2006

Immunohistochemical expression of Bcl-2, Bcl-x, and Bax in follicular carcinomas of the thyroid.

Bcl-2, bcl-x, and bax proteins are involved in the regulation of apoptosis. There is limited data on the expression of these proteins in follicular carcinomas (FCs) of the thyroid. A retrospective clinicopathologic review with bcl-2, bcl-x, and bax immunostaining of 34 FCs and 7 follicular adenomas with incomplete capsular penetration (FAICP) was performed. The study included 41 patients (25 females; age range 16 to 84 y, mean 50.9 y). All patients underwent surgical resection. Seven FC patients developed recurrent disease: 1 patient was alive (14.2 y) and 6 patients died with metastatic disease (mean survival 5.9 y). All remaining patients were disease-free (mean follow-up 7.9 y). Only one FAICP recurred (patient alive at 11 y). The remaining patients were disease-free (mean follow-up 6.9 y). Normal thyroid tissue stained positively for bcl-2 and bcl-x, and did not stain with bax. Only 15 tumors (12 FC and 3 FAICP) stained positively for bcl-2. None of the recurrent tumors demonstrated evidence of bcl-2 staining. The majority of tumors stained positively for bax (83%, 29 FC and 5 FAICP) and for bcl-x (93%, 32 FC and 6 FAICP); there was no correlation of staining with outcome. The majority of follicular neoplasms were positive for bax and negative for bcl-2 by immunohistochemistry. Aberrant expression of apoptosis-associated proteins may play a role in the pathogenesis of FC of the thyroid. All recurrent and fatal tumors were negative for bcl-2. These data suggest that the loss of bcl-2 expression may correlate with poorer prognosis.

Adenocarcinoma, Follicular↗
PubMed2006

Expression of cyclo-oxygenase-2 in ependymal tumors.

Up-regulation of cyclo-oxygenase-2 (COX-2), a cytokine-induced enzyme that metabolizes arachidonic acid into prostaglandins, has been described in some brain tumors, including astrocytomas. Little is known about its expression in ependymal neoplasms. The objective of the present study was to assess COX-2 immunostaining of ependymal tumors. Retrospective COX-2 immunohistochemical analysis was conducted on 117 ependymal tumors. Statistical analysis was performed using Student t-test. The study group (56 men and 44 women, mean age, 30.8 years) was comprised of 48 low-grade ependymomas (WHO grade II), 12 anaplastic ependymomas (WHO grade III), 27 myxopapillary ependymomas (WHO grade I) and 13 subependymomas (WHO grade I). At last known follow-up (range, 12-226 months; mean, 74 months), 52 patients were alive with no evidence of tumor, 16 patients were alive with residual tumor, nine patients died with tumor, one patient died with no tumor and three died with tumor status unknown. Nineteen patients had less than 12 months of follow-up. Thirty-six (36%) patients had tumors, which demonstrated positive COX-2 staining, including 16/27 (59%) myxopapillary ependymomas, 3/13 (23%) subependymomas, 14/48 (29%) ependymomas and 3/12 (25%) anaplastic ependymomas. Statistically significant COX-2 positive immunostaining was observed in myxopapillary ependymomas versus WHO grade II (P = 0.03) and grade III (P = 0.02) tumors. Increased COX-2 expression in myxopapillary ependymoma as compared to the WHO grade II and II ependymoma was observed. The reason for this apparent increased immunoexpression in these low-grade tumors is uncertain. COX-2 inhibitors may play a role in treatment of the subset of ependymal tumors that demonstrate increased expression. COX-2 staining did not reliably predict tumor behavior.

Adolescent↗
PubMed2006

Increased expression of 5-lipoxygenase in high-grade astrocytomas.

OBJECTIVE: 5-Lipoxygenase (5-LO) oxidizes arachidonic acid into proinflammatory eicosanoids that may promote tumorigenesis. In this study, we investigated whether 5-LO is expressed in human astrocytomas and what effect its expression may have on patient outcome. METHODS: Increased 5-LO messenger ribonucleic acid and protein expression was detected by the polymerase chain reaction and antibody-based approaches, respectively, in surgical astrocytoma specimens and established glioblastoma multiforme cell lines compared with primary cell culture from the human white matter. RESULTS: Immunohistochemical analysis revealed predominantly nuclear 5-LO staining in 44 of 49 glioblastoma multiforme samples (90%), 8 of 10 (80%) anaplastic astrocytomas samples, and 3 of 13 (23%) low-grade astrocytoma samples analyzed. Double-staining experiments with anti-CD-68 (macrophage/microglial marker) and anti-5-LO antibodies suggest that both CD-68-positive and CD-68-negative tumor cells express 5-LO protein. Staining of 5-LO was significantly more frequent in high-grade than in low-grade tumors (P = 0.001). Patients whose tumors expressed 5-LO were significantly older, had lower preoperative Karnofsky performance scores and shorter survival than patients whose tumors did not express 5-LO. After adjusting for pathological diagnosis and age, respectively, neither Karnofsky performance score nor survival were significantly associated with 5-LO staining. CONCLUSION: These data indicate that 5-LO is overexpressed in high-grade astrocytomas and supports the idea that eicosanoids may play a role in tumorigenesis of these brain tumors.

Adult↗
PubMed2006

Diagnostic yield associated with multiple simultaneous skeletal muscle biopsies.

Certain skeletal muscle disorders, such as inflammatory myopathies, may show regional variability, prompting consideration of simultaneous biopsy of more than 1 muscle to increase the likelihood of diagnosis. There are few data in the literature to support this approach. This study is a retrospective 8-year review of 99 cases (52 men; mean age, 61.8 years) who had multiple muscles biopsied simultaneously. The most common clinical symptoms prompting biopsy included weakness in 83 cases and myalgia in 15. The most common diagnoses were as follows: neurogenic atrophy, 48; inflammatory myopathy, excluding inclusion body myositis, 29; and type II muscle fiber atrophy, 24. Diagnoses were the same in both biopsied muscles in 54 cases (55%). In 17 cases, a diagnosis was made from only 1 biopsy. Of 29 inflammatory myopathies and vasculitis (excluding inclusion body myositis), a diagnosis could be made from only 1 of the 2 biopsies in 10 cases (34%). In a significant subset of cases, a potentially treatable inflammatory myopathic condition might have been missed if only 1 site had been biopsied, justifying biopsy of 2 sites in suspected cases of inflammatory myopathy.

Adult↗
PubMed2006

The impact of genotype on outcome in oligodendroglioma: validation of the loss of chromosome arm 1p as an important factor in clinical decision making.

OBJECT: Oligodendrogliomas are rare primary brain tumors. They comprise approximately 5 to 33% of all glial tumors but differ from astrocytomas by being associated with a more favorable prognosis, making their correct identification important. Allelic loss of chromosome arms 1p and 19q is found in a substantial subpopulation of tumors with an oligodendroglioma phenotype. Anaplastic oligodendrogliomas with allelic loss of 1p have been associated with chemosensitivity and a longer patient survival period. METHODS: Oligodendroglial neoplasms were studied using fluorescence in situ hybridization of formalin-fixed, paraffin-embedded tissue specimens; reference and target probe sets were used to map the telomeric regions of 1p and 19q. The results were correlated with the clinical characteristics of patients treated at our institution between 1993 and 2003. Data obtained in 96 patients were analyzed. This included 63 patients (65.6%) with World Health Organization (WHO) Grade II oligodendroglioma, 22 (23%) with Grade III oligodendroglioma, and 11 (11.4%) with mixed oligoastrocytoma. Analysis of 1p in patients with pure oligodendroglioma revealed a loss of 1p in 42 patients (49.4%). In 46 of these patients 19q was lost and in 70 (82.3%) there was concordance for combined loss or retention of both 1p and 19q (p < 0.0001). Patients with oligodendroglioma in whom a loss of 1p was present fared significantly better, and this outcome was unrelated to the treatment modality or WHO grade, compared with patients in whom 1p was intact (p < 0.05). CONCLUSIONS: To the authors' knowledge, this study includes the largest published series of WHO Grade II oligodendroglioma and 1p analysis. The results suggest that the association between long-term survival and 1p loss in oligodendroglioma is unrelated to treatment. The authors of further prospective studies may better determine the true value of the allelic loss of 1p and its implication for clinical decision making.

Adolescent↗
PubMed2006

Concurrent lymphocytic hypophysitis and pituitary adenoma. Case report and review of the literature.

Lymphocytic hypophysitis (LyH) is an uncommon intrasellar lesion characterized by lymphocytic infiltration of the adenohypophysis. Evidence suggests that the cause is autoimmune, and the symptoms are usually related to either a mass effect or endocrine dysfunction. Lymphocytic hypophysitis has been described rarely in the setting of other simultaneous pathological processes that involve the pituitary and sella turcica, and is postulated to arise from an intrinsic inflammatory response. The authors report the case of a 43-year-old woman who presented with a 2-month history of galactorrhea and pseudohyperprolactinemia secondary to a 10-mm lesion within an enlarged pituitary gland. She was nulliparous and had no contributory medical history. Serial neuroimaging performed over a 2-year period demonstrated lesion growth, and visual deficits had developed; together these warranted surgical intervention. A transsphenoidal resection was performed. Microscopic and immunohistopathological examinations revealed a nonsecreting pituitary adenoma with concurrent lymphocytic adenohypophysitis. This is the first documented case of LyH in the setting of a null-cell pituitary adenoma. The authors review the related literature and outline potential mechanisms for the concurrent development of LyH and a pituitary adenoma.

Adenoma↗
PubMed2006

An algorithmic approach to the brain biopsy--part I.

CONTEXT: The formulation of appropriate differential diagnoses for a slide is essential to the practice of surgical pathology but can be particularly challenging for residents and fellows. Algorithmic flow charts can help the less experienced pathologist to systematically consider all possible choices and eliminate incorrect diagnoses. They can assist pathologists-in-training in developing orderly, sequential, and logical thinking skills when confronting difficult cases. OBJECTIVE: To present an algorithmic flow chart as an approach to formulating differential diagnoses for lesions seen in surgical neuropathology. DESIGN: An algorithmic flow chart to be used in teaching residents. RESULTS: Algorithms are not intended to be final diagnostic answers on any given case. Algorithms do not substitute for training received from experienced mentors nor do they substitute for comprehensive reading by trainees of reference textbooks. Algorithmic flow diagrams can, however, direct the viewer to the correct spot in reference texts for further in-depth reading once they hone down their diagnostic choices to a smaller number of entities. The best feature of algorithms is that they remind the user to consider all possibilities on each case, even if they can be quickly eliminated from further consideration. CONCLUSIONS: In Part I, we assist the resident in learning how to handle brain biopsies in general and how to distinguish nonneoplastic lesions that mimic tumors from true neoplasms.

Algorithms↗
PubMed2006

An algorithmic approach to the brain biopsy--part II.

CONTEXT: The formulation of appropriate differential diagnoses for a slide is essential to the practice of surgical pathology but can be particularly challenging for residents and fellows. Algorithmic flow charts can help the less experienced pathologist to systematically consider all possible choices and eliminate incorrect diagnoses. They can assist pathologists-in-training in developing orderly, sequential, and logical thinking skills when confronting difficult cases. OBJECTIVE: To present an algorithmic flow chart as an approach to formulating differential diagnoses for lesions seen in surgical neuropathology. DESIGN: An algorithmic flow chart to be used in teaching residents. RESULTS: Algorithms are not intended to be final diagnostic answers on any given case. Algorithms do not substitute for training received from experienced mentors nor do they substitute for comprehensive reading by trainees of reference textbooks. Algorithmic flow diagrams can, however, direct the viewer to the correct spot in reference texts for further in-depth reading once they hone down their diagnostic choices to a smaller number of entities. The best feature of algorithms is that they remind the user to consider all possibilities on each case, even if they can be quickly eliminated from further consideration. CONCLUSIONS: In Part II, we assist the resident in arriving at the correct diagnosis for neuropathologic lesions containing granulomatous inflammation, macrophages, or abnormal blood vessels.

Algorithms↗
PubMed2006

Multiorgan involvement in nephrogenic fibrosing dermopathy: an autopsy case and review of the literature.

Nephrogenic fibrosing dermopathy is a recently recognized, scleromyxedema-like fibrosing skin condition that occurs in individuals with acute or chronic renal failure. Although the early descriptions of this disorder describe a purely cutaneous disease process, 2 recent autopsy reports have identified apparent multiorgan fibrosis with involvement of skeletal muscle, myocardium, lungs, kidneys, and testes. We describe a 23-year-old man with nephrogenic fibrosing dermopathy and significant fibrosis of the atrial myocardium and dura mater, which was identified at autopsy. Dural fibrosis is a previously undescribed systemic manifestation of nephrogenic fibrosing dermopathy. The literature is reviewed.

Adult↗
PubMed2005

Long-term survival and functional status of patients with low-grade astrocytoma of spinal cord.

PURPOSE: To determine survival and changes in neurologic function and Karnofsky performance status (KPS) in a series of patients treated for low-grade astrocytoma of the spinal cord during the past two decades. METHODS: This study consisted of 14 patients with pathologically confirmed low-grade astrocytoma of the spinal cord who were treated between 1980 and 2003. All patients underwent decompressive laminectomy followed by biopsy (n = 7), subtotal resection (n = 6), or gross total resection (n = 1). Ten patients underwent postoperative radiotherapy (median total dose 50 Gy in 28 fractions). The overall survival, progression-free survival, and changes in neurologic function and KPS were measured. RESULTS: The overall survival rate at 5, 10, and 20 years was 100%, 75%, and 60%, respectively. The progression-free survival rate at 5, 10, and 20 years was 93%, 80%, and 60%, respectively. Neither overall survival nor progression-free survival was clearly correlated with any patient, tumor, or treatment factors. Neurologic function and KPS worsened after surgery in 8 (57%) of 14 and 9 (69%) of 13 patients, respectively. At a mean follow-up of 10.2 years, neurologic function had stabilized or improved in 8 (73%) of 11 remaining patients, but the KPS had worsened in 5 (50%) of 10. Most patients who were employed before surgery were working at last follow-up. CONCLUSION: Patients who undergo gross total resection of their tumor may be followed closely. Patients who undergo limited resection should continue to receive postoperative RT (50.4 Gy in 1.8-Gy fractions). The functional measures should be routinely evaluated to appreciate the treatment outcomes.

Adult↗
PubMed2005

The NMDA receptor NR2B subunit contributes to epileptogenesis in human cortical dysplasia.

Cortical dysplasia (CD) is often associated with pharmacoresistant epilepsy. Previous studies showed increased expression of the NMDA receptor subunit NR2B in dysplastic and epileptic human neocortex. We tested the hypothesis that differential increase of NR2B constitutes an epileptogenic mechanism in humans. Dysplastic neocortex and lateral temporal lobe regions resected for treatment of pharmacoresistant seizures were processed for electrophysiological, histological, and immunocytochemical studies. Assignment to the "dysplastic" (n = 8) and "non-dysplastic" (n = 8) groups was based on histology. Neurons in "dysplastic" samples differentially stained for NR2B. Western blot (n = 6) showed an immunoreactive band for NR2B in three out of four "dysplastic" samples. Epileptiform field potentials (EFP) were elicited in vitro by omission of magnesium from the bath. EFP in "dysplastic" slices were characterized by multiple afterdischarges, occurring at a significantly higher repetition rate than EFP in non-dysplastic slices. The NR2B-specific NMDA receptor inhibitor ifenprodil (10muM) suppressed EFP in dysplastic slices. In non-dysplastic slices, burst repetition rate did not change with ifenprodil application. In both dysplastic and non-dysplastic slices, EFP were suppressed by a non-specific NMDAR antagonist (APV) or AMPA receptor antagonist (CNQX). These results provide additional evidence that the differential expression of NR2B in dysplastic human neocortex may play a role in the expression of in-situ epileptogenesis in human CD. NR2B may constitute a target for new diagnostic and pharmacotherapeutic approaches.

Adolescent↗