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Biomedical subjects

A Perry

Publications and source records attributed to A Perry.

At least 73 records · Page 4Linked to original sources
PubMed1999

Analysis of oncogene and tumor suppressor gene alterations in pediatric malignant astrocytomas reveals reduced survival for patients with PTEN mutations.

Although common among adult intracranial neoplasms, pediatric malignant astrocytomas (PMAs) comprise a relatively small proportion of the brain tumors that occur in children. The scarcity of such cases generally requires that molecular analyses of PMAs are based on the utilization of paraffin-embedded material, and here we have used 39 such specimens to examine the incidence and prognostic significance of oncogene and tumor suppressor gene alterations (including amplifications of EGFR, CDK4, and MDM2 as well as inactivating mutations of CDKN2A, TP53, and PTEN) in these tumors. In general, the frequency of alteration for the genes we have studied fell within ranges that have been reported for adult astrocytomas. However, EGFR amplification, which is usually observed in approximately 40% and 15% of adult grade 4 and grade 3 astrocytomas, respectively, was not detected in any member of this series. With regard to prognosis, PTEN mutations were significantly associated with decreased survival among grade 3 and grade 4 PMA patients, a potentially important observation because neither patient age nor tumor malignancy grade was correlated with outcome for these individuals. In total, our data suggest at least one significant distinction between the genetic etiology of pediatric and adult astrocytomas and additionally reveal that analysis of PTEN mutations in PMA patients may be useful in the differential diagnosis of these tumors.

Adolescent↗
PubMed1998

The prognostic significance of MIB-1, p53, and DNA flow cytometry in completely resected primary meningiomas.

BACKGROUND: Despite the availability of clinical and pathologic parameters of prognosis, the behavior of an individual meningioma may be difficult to predict. In a recent review of gross totally resected (GTR) meningiomas, the authors found strong associations between microscopic brain invasion, increased mitotic rate (> or = 4/10 high-power fields), the presence of at least 3 of 4 morphologic variables (sheeting, hypercellularity, macronucleoli, and small cells), and decreased recurrence free survival (RFS). In this study, they assessed the prognostic value of three ancillary techniques: DNA flow cytometry, MIB-1 labeling, and p53 protein expression. METHODS: The authors evaluated primary GTR meningiomas from 425 patients with DNA flow cytometry, immunostaining for MIB-1, and determination of p53 protein expression. The patients were followed until death or for a median of 8.9 years. RESULTS: An MIB-1 labeling index (LI) of > or = 4.2%, identified in 8% of cases, was strongly associated with decreased RFS in univariate analysis (P=0.0001). Fourteen percent contained aneuploid cell populations, and 48% exhibited a p53 LI of >10%. Neither variable was associated with decreased RFS. Further analysis revealed a close association between MIB-1 LI and mitotic index, the latter being the parameter of greatest significance in multivariate analysis. CONCLUSIONS: MIB-1 LI is a useful adjunct to routine histologic evaluation of meningiomas and appears to be of greatest value in the evaluation of tumors exhibiting borderline atypia. In contrast, our data suggest that, regarding patients with primary GTR meningiomas, neither flow cytometry nor p53 immunohistochemistry provides useful prognostic information.

Adolescent↗
PubMed1998

A study of interrater reliability when using videofluoroscopy as an assessment of swallowing.

Videofluoroscopic assessment of swallowing is widely used in clinical settings. The interpretation of such assessments depends on subjective visual judgments but the reliability of these judgments has been poorly researched. This study measured interrater reliability of judgments, made by speech pathologists, of videofluoroscopic images of subjects swallowing liquid and semisolid boluses. A 5-point rating scale was used in three conditions: individually after careful reading; together with other speech pathologists in group discussion; and individually after the group discussion. Analysis of the ratings for the three conditions revealed that the level of agreement among raters was generally higher for semisolid swallows than for liquid swallows. The highest levels of agreement occurred for ratings made after group discussions. The levels of agreement were lowest when raters worked alone, relying only on reading the scale. Individual rating after group discussion resulted in higher levels of agreement than sole reliance on reading the scale. Factors influencing the levels of interrater agreement, including the timing of observations, bolus consistency, the quality of the image, and the complexity of the task, are discussed.

Deglutition↗
PubMed1998

Population structure of nuclear and mitochondrial DNA variation among humpback whales in the North Pacific.

The population structure of variation in a nuclear actin intron and the control region of mitochondrial DNA is described for humpback whales from eight regions in the North Pacific Ocean: central California, Baja Peninsula, nearshore Mexico (Bahia Banderas), offshore Mexico (Socorro Island), southeastern Alaska, central Alaska (Prince Williams Sound), Hawaii and Japan (Ogasawara Islands). Primary mtDNA haplotypes and intron alleles were identified using selected restriction fragment length polymorphisms of target sequences amplified by the polymerase chain reaction (PCR-RFLP). There was little evidence of heterogeneity in the frequencies of mtDNA haplotypes or actin intron alleles due to the year or sex composition of the sample. However, frequencies of four mtDNA haplotypes showed marked regional differences in their distributions (phi ST = 0.277; P < 0.001; n = 205 individuals) while the two alleles showed significant, but less marked, regional differences (phi ST = 0.033; P < 0.013; n = 400 chromosomes). An hierarchical analysis of variance in frequencies of haplotypes and alleles supported the grouping of six regions into a central and eastern stock with further partitioning of variance among regions within stocks for haplotypes but not for alleles. Based on available genetic and demographic evidence, the southeastern Alaska and central California feeding grounds were selected for additional analyses of nuclear differentiation using allelic variation at four microsatellite loci. All four loci showed significant differences in allele frequencies (overall FST = 0.043; P < 0.001; average n = 139 chromosomes per locus), indicating at least partial reproductive isolation between the two regions as well as the segregation of mtDNA lineages. Although the two feeding grounds were not panmictic for nuclear or mitochondrial loci, estimates of long-term migration rates suggested that male-mediated gene flow was several-fold greater than female gene flow. These results include and extend the range and sample size of previously published work, providing additional evidence for the significance of genetic management units within oceanic populations of humpback whales.

Alleles↗
PubMed1998

The effect of dietary creatine supplementation on skeletal muscle metabolism in congestive heart failure.

AIMS: To assess the effects of dietary creatine supplementation on skeletal muscle metabolism and endurance in patients with chronic heart failure. METHODS: A forearm model of muscle metabolism was used, with a cannula inserted retrogradely into an antecubital vein of the dominant forearm. Maximum voluntary contraction was measured using handgrip dynanometry. Subjects performed handgrip exercise, 5 s contraction followed by 5 s rest for 5 min at 25%, 50%, and 75% of maximum voluntary contraction or until exhaustion. Blood was taken at rest and 0 and 2 min after exercise for measurement of lactate and ammonia. After 30 min the procedure was repeated with fixed workloads of 7 kg, 14 kg and 21 kg. Patients were assigned to creatine 20 g daily or matching placebo for 5 days and returned after 6 days for repeat study. RESULTS: Contractions (median (25th, 75th interquartiles)) until exhaustion at 75% of maximum voluntary contraction increased after creatine treatment (8 (6, 14) vs 14 (8, 17), P = 0.025) with no significant placebo effect. Ammonia per contraction at 75% maximum voluntary contraction (11.6 mumol/l/contraction (8.3, 15.7) vs 8.9 mumol/l/contraction (5.9, 10.8), P = 0.037) and lactate per contraction at 75% maximum voluntary contraction (0.32 mmol/l/contraction (0.28, 0.61) vs 0.27 mmol/l/contraction (0.19, 0.49), P = 0.07) fell after creatine but not after placebo. CONCLUSIONS: Creatine supplementation in chronic heart failure augments skeletal muscle endurance and attenuates the abnormal skeletal muscle metabolic response to exercise.

Aged↗
PubMed1998

"Rhabdoid" meningioma: an aggressive variant.

It is has been suggested that rhabdoid morphology is associated with a poor prognosis, regardless of tumor histogenesis. We report a series of 15 meningiomas with rhabdoid features. Nine patients had undergone multiple resections. In six, the rhabdoid component was histologically apparent only in recurrences. Rhabdoid morphology was defined as sheets of loosely cohesive cells with eccentric nuclei and hyaline, paranuclear inclusions. Ultrastructurally, the latter consisted of whorls of intermediate filaments often entrapping lysosomes or other organelles. Meningothelial features included whorl formation and nuclear pseudoinclusions, immunohistochemical coexpression of vimentin and epithelial membrane antigen, and the ultrastructural finding of interdigitating cell membranes and intercellular junctions. At the histologic level, a conventional meningioma component was noted in most tumors; only four lesions were entirely rhabdoid. Histologic malignancy (brain invasion or anaplasia) was observed in nine cases, another two tumors being considered malignant on the basis of extracranial metastasis. In the majority, increased cell proliferation was evidenced by a high mitotic rate or MIB-1 LI. At last follow-up, 13 patients (87%) had experienced at least one recurrence and 8 (53%) were dead of disease. Median time to death was 5.8 years after initial surgery and 3.1 years after the first appearance of rhabdoid morphology. Our findings corroborate those from a smaller series recently reported by Kepes et al. on the same entity (Kepes JJ, Moral LA, Wilkinson SB, Abdullah A, Llena JF. Rhabdoid transformation of tumor cells in meningiomas: A histologic indication of increased proliferative activity. Report of four cases. Am J Surg Pathol 1998;22:231-8). They further suggest that rhabdoid meningiomas are highly aggressive tumors and that the rhabdoid phenotype represents a marker of malignant transformation in meningiomas.

Adolescent↗
PubMed1998

"Value" of improved treadmill exercise capacity: lessons from a study of rate responsive pacing.

OBJECTIVES: To compare the value of a series of cardiovascular measurements in patients with symptomatic disease receiving an effective treatment (rate responsive pacing). PATIENTS: 12 pacemaker dependent patients with VVIR units. INTERVENTIONS: Single blind crossover between VVI and VVIR. OUTCOME MEASURES: Exercise capacity was assessed by treadmill tests (modified Bruce protocol and a fixed workload protocol) with respiratory gas analysis. Self paced corridor walk tests were also undertaken. Quality of life (QOL) was assessed by questionnaire. Daily activity was measured in the patients' homes using shoe and belt pedometers. RESULTS: Treadmill tests and QOL questionnaires correctly identified the clinical benefit associated with VVIR. The modified Bruce protocol was superior to the fixed workload protocol as it was better tailored to the fairly well preserved exercise capacity of the patients. Symptom scores, but not walking times, were improved with VVIR during corridor walk tests. VVIR did not improve daily activity measured using either the belt or shoe pedometers. CONCLUSIONS: VVIR pacing improved some but not all measures of exercise capacity. This finding illustrates the difficulty of selecting an instrument to measure symptomatic improvement in clinical research; and raises the question, what is the best way of measuring exercise capacity?

Activities of Daily Living↗
PubMed1998

Synthesis and evaluation of some masked phosphate esters of the anti-herpesvirus drug 882C (netivudine) as potential antiviral agents.

A number of symmetric and asymmetric 5'-phosphate esters of the potent anti-varicella-zoster virus (VZV) agent 1-(beta-D-arabinofuranosyl)-5-prop-1-ynyluracil (882C; netivudine) were prepared as potential lipophilic, membrane-soluble prodrugs of the bio-active phosphate forms. The compounds were prepared by the base-catalysed coupling of various phosphorochloridates with the free nucleoside analogue. Compounds were fully characterized by a range of spectroscopic and analytical methods and were studied for their inhibition of several viruses in tissue culture. All of the phosphate esters were inactive against human cytomegalovirus, herpes simplex virus type 2, VZV, human immunodeficiency virus type 1 and influenza A virus (EC50 > 100 microM) except the 5'-(4-nitrophenyl phenyl) phosphate, which inhibited influenza A virus. The relative rate of esterase-mediated hydrolysis of one of the lead target structures was measured in order to rationalize the poor antiviral action, and data were collected on possible metabolites in support of this analysis. Cell-specific esterases are implicated as key determinants of the antiviral potency of prodrugs of this type.

Animals↗
PubMed1998

Competencies of liberal education in post-RN baccalaureate students: a longitudinal study.

The purpose of this longitudinal study was to examine the relationship among liberal education competencies as demonstrated in the professional and personal lives of post-RN students and time spent in a BScN program. The six competencies identified by Dressel (1979) and used by Bottoms (1988) to define the liberally educated person provided the framework for this study. The Dressel competencies have been validated in the literature as being representative of the universe of competencies that are anticipated outcomes of baccalaureate nursing education. Results indicated that after 5 years of part-time study at the baccalaureate level, significant differences were found in the competencies of liberal education as demonstrated in the professional and personal lives of post-RN learners. The competencies as demonstrated in the professional lives of post-RN learners developed consistently over time, while the development of competencies as demonstrated in the personal lives of learners lagged behind. The study contributes to the small but growing body of literature which explores the impact of a liberal education on post-RN learners.

Canada↗
PubMed1998

Primarily resected meningiomas: outcome and prognostic factors in 581 Mayo Clinic patients, 1978 through 1988.

OBJECTIVE: To establish prognostic factors for recurrence and outcome of surgical treatment, with or without postoperative radiation therapy, in patients with meningiomas. MATERIAL AND METHODS: From 1978 through 1988, 581 patients underwent initial resection of a previously untreated primary meningioma at Mayo Clinic Rochester. In this study cohort, the outcome and prognostic factors associated with radiographic progression-free survival were analyzed. RESULTS: Gross total resection (GTR) of the meningioma was accomplished in 80% of patients; the other 20% underwent less than GTR. Perioperative mortality within 10 days was 1.6%. Overall survival was significantly decreased from that for an age- and sex-matched cohort from the US white population. Progression-free survival at 5 and 10 years was 88% and 75%, respectively, in patients who underwent GTR and 61% and 39%, respectively, in those who underwent less than GTR. Multivariate analysis showed that age younger than 40 years, male sex, less than GTR, optic nerve involvement, and 4 or more mitotic figures per 10 high-power fields were associated with decreased progression-free survival. The 581 patients had 106 first recurrences. A trend toward improved progression-free survival was noted after first recurrence when irradiation with or without operation was used in comparison with only surgical treatment (P = 0.058). CONCLUSION: With only operative treatment of meningioma, the 10-year recurrence rate was 25% in patients who had GTR and 61% in those who had less than GTR. These results emphasize the need for long-term follow-up and for consideration of adjuvant radiation therapy. Patients treated at the time of recurrence seem to benefit from radiation therapy with or without surgical resection. Factors associated with recurrence were (1) less than GTR, (2) involvement of the anterior visual pathway, (3) age younger than 40 years, and (4) increased mitotic index.

Adolescent↗
PubMed1998

Capitating home health care.

Managed care is beginning to make inroads into home health care, and more home healthcare providers are signing capitation contracts. Unfortunately, a lack of home healthcare cost and utilization data has made it difficult to set reasonable capitation rates. In addition, home healthcare providers currently have little control over care management and, therefore, cannot effectively manage utilization under capitation. They also are unused to thinking in terms of controlling utilization and guaranteeing services for a predetermined population at a preset price. In the long run, however, home healthcare providers and payers that develop cooperative working relationships will find ways to collect and share the information they need to make these arrangements mutually successful.

Capitation Fee↗
PubMed1998

The effects of thiazide diuretics on bone mineral metabolism.

Thiazide diuretics cause changes in calcium metabolism. Clinically, these changes include a decreased excretion of calcium, and in some instances, this results in a corresponding increase in bone mineral. The study of mineral metabolism in bone is difficult because of the slow turnover rate of bone. For this reason, the rat fracture model was used to study bone mineral metabolism in animals given thiazide diuretics. Fifty rats were divided into four groups: group 1 received a fracture of the right tibia and thiazide diuretics, group 2 received thiazide and no fracture, group 3 received no drugs and a fracture, and group 4 received no drugs and no fracture. At the end of 35 days postinjury, all animals were sacrificed. Biochemical and biomechanical results were analyzed, and revealed that animals that received thiazide diuretics and a fracture had the highest bone mineral content.

Animals↗
PubMed1998

Anterior visual pathway meningiomas primarily resected between 1978 and 1988: the Mayo Clinic Rochester experience.

The relapse rate, overall survival, and factors associated with a decreased recurrence-free survival rate in patients with anterior visual pathway (AVP) meningioma were compared with these features in patients who had meningiomas at other sites. Management of these patients is discussed. A review of the records of 581 consecutive patients who had primary resection of meningiomas between 1978 and 1988 identified 43 patients with AVP meningioma. Multiple clinical, surgical, and pathologic factors at the initial examination were analyzed to assess their association with recurrence, and the patients who had AVP meningioma were compared with patients who had non-AVP meningiomas to determine the factors that may influence recurrence. Recurrence-free and overall survival rates were determined. The AVP tumors were associated with a higher rate of recurrence. Subtotal resection was more common in the AVP tumors, but it alone was not associated with the decrease in recurrence-free or overall survival rates. Several factors that may explain the higher recurrence rate in patients with AVP meningioma were identified. Anterior visual pathway meningioma is associated with a higher rate of recurrence than are meningiomas at other sites. Operation remains the mainstay of treatment for symptomatic nonseeing eyes. Radiation therapy seems to be effective for managing recurrent tumor.

Adolescent↗
PubMed1997

Metastatic adenocarcinoma to the brain: an immunohistochemical approach.

The diagnosis of metastatic adenocarcinoma to the brain of unknown primary is problematic, and the role of immunohistochemistry in identifying a source has not been fully characterized. Sixty-eight metastatic adenocarcinomas of the brain with known primaries were immunostained with antibodies to cytokeratin 7 (CK7), cytokeratin 20 (CK20), CAM 5.2, wide-spectrum keratin (WSK), gross cystic disease fluid protein-15 (GCDFP-15), glial fibrillary acidic protein (GFAP), estrogen receptor (ER), and progesterone receptor (PR). True positive staining was defined as CK7 in lung or breast; CK20 in gastrointestinal; and GCDFP-15, ER, and PR in breast carcinomas. CK7 immunoreactivity was present in all 27 lung carcinomas and 14 of 15 breast carcinomas with a sensitivity of 98% and specificity of 78%. CK20 stained 15 of 16 GI carcinomas with a sensitivity and specificity of 94%. None of the cytokeratins stained surrounding brain tissue. GCDFP-15, ER, and PR had sensitivities of 33%, 33%, and 87%, with specificities of 92%, 84%, and 28%, respectively. PR often stained nuclei of normal brain tissue and was accentuated in areas of necrosis or cautery artifact. CK7 and CK20 are highly sensitive and specific in patients with metastatic adenocarcinoma to the brain of unknown primary. GCDFP-15 and ER are relatively specific, but insensitive markers, and PR is nonspecific and difficult to interpret.

Adenocarcinoma↗
PubMed1997

Change in CD4+ cell enumeration following aerobic exercise training in HIV-1 disease: possible mechanisms and practical applications.

Growing evidence suggests that routine physical activity, by individuals who are HIV-1 infected, may have significant impact on several important components of good health. Some of the physical benefits noted are: an increase in cardiopulmonary fitness, improved muscle function, and weight gain, while psychological benefits consisting of improved mood states and increased active coping behaviors have been observed. However, the emphasis of this paper is on the effects of exercise training on the enumeration of CD4+ cells in HIV/AIDS. A review of all the available literature revealed: (1) no decline in CD+ cell counts seen in any of the studies, regardless of the initial stage of disease, level of CD4+ cells, or symptomatology; (2) a trend toward an increase in the number of CD4+ cells in all but one study, with the more significant increases seen in those subjects at earlier stages of disease; and (3) the importance of homogeneous study samples when investigating the effects of exercise in a dynamic disease, such as HIV/AIDS. With regard to possible mechanisms, psychological stress has been implicated among the cofactors contributing to the immunological decline in HIV-1 disease. Good evidence was presented which supports the stress management role of exercise training as a means to explain the buffering of these suppressive stressor effects, thereby facilitating a return of the CD4+ cell count to more normal levels. We therefore believe that the observed elevation in the number of CD4+ cells actually represents a normalization of CD4+ cells. With regards to practical application, collectively these studies provide reason to encourage HIV-1 infected individuals to begin an exercise training program, preferably while they are in the early stages of disease, and in compliance with the suggested guidelines.

Acquired Immunodeficiency Syndrome↗