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Biomedical subjects

A Perry

Publications and source records attributed to A Perry.

At least 55 records · Page 3Linked to original sources
PubMed2000

Measuring the costs and benefits of heart disease monitoring.

OBJECTIVE: To evaluate the costs and benefits of alternative systems of coronary heart disease monitoring in Scotland. DESIGN: An option appraisal was conducted to evaluate the costs and benefits of implementing a coronary heart disease monitoring system. This involved a review of existing Scottish datasets and relevant reports, specification of options, definition and weighting of benefit criteria by key stakeholders, assessment of options by experts, and costing of options. The options were assessed by 33 stakeholders (grouped as cardiologists, patient representatives, general practitioners, public health physicians, and policy makers), plus 13 topic experts. SETTING: Scotland (population 5.1 million). RESULTS: Between group mean benefit weights were: mortality rates and case fatality (10.6), quality of life (9.8), patient function (8.8), hospital activity (7.8), primary care activity (9.25), prescribing (5.72), socioeconomic impact (4.0), risk factors (7.4), prevalence (5.0), incidence (6.0), case registration (6.82), international comparability (4.2), breadth of coverage (8.8), and frequency (5.8). Differences between group weights were significant for prevalence (p = 0.048) and international comparability (p = 0.032). Four monitoring options were identified: a community epidemiology model, based on MONICA (monitoring trends and determinants in cardiovascular disease) study methodology applied to a series of eight representative communities, had the highest benefits, at an average annual discounted cost of approximately pound 360,000; models based on the Australian cardiovascular disease monitoring scheme and on enhanced routine data offered fewer benefits at discounted average annual costs ranging from pound 165,000 to pound 195,000; finally, a coronary heart disease registry modelled on the Scottish Cancer Registry scheme would have had fewer benefits and substantially higher costs than the other options. CONCLUSIONS: The most beneficial coronary heart disease monitoring system is the community epidemiology model, based on MONICA methodology. Option appraisal potentially offers an explicit and transparent methodology for evidence based policy development.

Coronary Disease↗
PubMed2000

Alterations of chromosome arms 1p and 19q as predictors of survival in oligodendrogliomas, astrocytomas, and mixed oligoastrocytomas.

PURPOSE: A recent report suggests that alterations of chromosome arms 1p and 19q are associated with chemotherapeutic response and overall survival in anaplastic oligodendroglioma patients treated with procarbazine, lomustine, and vincristine chemotherapy. We set out to further clarify the diagnostic and prognostic implications of these alterations in a broader set of diffuse gliomas, including astrocytic neoplasms and low-grade oligodendrogliomas. PATIENTS AND METHODS: Fluorescence in situ hybridization (FISH) signals from DNA probes mapping to 1p and 19q common deletion regions were enumerated in 162 diffuse gliomas (79 astrocytomas, 52 oligodendrogliomas, and 31 mixed oligoastrocytomas), collected as part of an ongoing prospective investigation of CNS tumors. RESULTS: The oligodendroglial phenotype was highly associated with loss of 1p (P =.0002), loss of 19q (P <.0001), and combined loss of 1p and 19q (P <.0001). Combined loss of 1p and 19q was identified as a univariate predictor of prolonged overall survival among patients with pure oligodendroglioma (log-rank, P =.03) and remained a significant predictor after adjusting for the effects of patient age and tumor grade (P <.01). This favorable association was not evident in patients with astrocytoma or mixed oligoastrocytoma. CONCLUSION: Combined loss of 1p and 19q is a statistically significant predictor of prolonged survival in patients with pure oligodendroglioma, independent of tumor grade. Given the lack of this association in patients with astrocytic neoplasms and the previously demonstrated chemosensitivity of oligodendrogliomas, a combined approach of histologic and genotypic assessment could potentially improve existing strategies for patient stratification and management.

Adolescent↗
PubMed2000

Medulloblastomas with extensive posttherapy neuronal maturation. Report of two cases.

The authors report on two patients with classic medulloblastoma, each of whom underwent extensive therapy-associated neuronal maturation. The first patient presented at 3 months of age with hydrocephalus caused by a 5-cm tumor in the cerebellar vermis. He underwent a gross-total resection of a desmoplastic medulloblastoma. No mature elements were identified. Despite adjuvant chemotherapy, a 1.5-cm recurrent tumor developed 6 months later. Sections from the subtotally resected tumor demonstrated exclusively mature neuronal elements, ranging from neurocytes to ganglion cells. Four months later, a second recurrent tumor was resected. The specimen collected this time demonstrated classic medulloblastoma morphological characteristics. The patient was subsequently treated with radiation therapy, which seemed to have an effect; however, the tumor eventually progressed and the patient died. The second patient presented at 3 years of age with a midline medulloblastoma and was treated with subtotal resection, radiation therapy, and chemotherapy. Although the tumor remained stable on radiographic imaging, a second resection was performed 8 years later to alleviate hydrocephalus. Histological examination revealed predominantly small mature neurons with scattered ganglion cells and extensive calcification. No adjuvant therapy was given and the patient is alive and well as of his last follow-up examination. The mature neuronal neoplasms resected in both patients demonstrated negligible proliferative indices and stained appropriately with neuronal immunohistochemical markers. The smaller neuronal population resembled those of a central neurocytoma and medullocytoma/cerebellar neurocytoma. Analogous to neuroblastoma, our cases suggest that adjuvant therapy can induce extensive or complete neuronal maturation in medulloblastoma. Additional cases must be studied to determine the prognostic significance of this rare phenomenon.

Adolescent↗
PubMed1999

Clinicopathologic study of 85 similarly treated patients with anaplastic astrocytic tumors. An analysis of DNA content (ploidy), cellular proliferation, and p53 expression.

BACKGROUND: The biologic behavior of anaplastic (World Health Organization Grade III) astrocytomas and oligoastrocytomas is highly variable, ranging from rapid progression to prolonged survival. It is difficult to predict the outcome of an individual patient based on morphology alone. METHODS: To determine the prognostic value of commonly used clinicopathologic markers, we reviewed our experience with 85 similarly treated patients enrolled in 3 North Central Cancer Treatment Group high grade glioma protocols. The pathology was comprised exclusively of primary anaplastic astrocytic tumors (66 astrocytomas and 19 oligoastrocytomas). Variables examined included patient age, morphologic type, preoperative performance score, extent of surgery, solitary versus multiple mitoses, DNA flow cytometric and image morphometric parameters, and expression of proliferating cell nuclear antigen, MIB-1, and p53 expression. RESULTS: The study was comprised of 48 men and 37 women ranging in age from 14-79 years (median age, 47 years). Overall survival ranged from <1 month to >12 years (median, 21.6 months). Statistical analyses revealed that age accounted for the majority of this extensive variability in survival. The median survival times were 65. 5 months, 22.1 months, and 4.4 months, respectively, for the groups <40 years, 40-59 years, and >/=60 years, respectively (P < 0.0001). On univariate analyses, aneuploidy by flow cytometry and a low performance score also predicted a better survival (P values of 0.04 and 0.009, respectively). Statistical trends predicting a better survival were observed for patients with a solitary mitosis and p53 immunopositivity. However, only patient age remained significant in multivariate models. CONCLUSIONS: In a small but relatively uniformly treated cohort of patients with anaplastic astrocytomas and oligoastrocytomas, patient age was associated strongly and inversely with overall survival. Once patient age was taken into account, the clinical and pathologic markers tested appeared to be of limited prognostic value.

Adolescent↗
PubMed1999

Localization of common deletion regions on 1p and 19q in human gliomas and their association with histological subtype.

Allelic alterations of chromosomes 1 and 19 are frequent events in human diffuse gliomas and have recently proven to be strong predictors of chemotherapeutic response and prolonged survival in oligodendrogliomas (Cairncross et al., 1998; Smith et al., submitted). Using 115 human diffuse gliomas, we localized regions of common allelic loss on chromosomes 1 and 19 and assessed the association of these deletion intervals with glioma histological subtypes. Further, we evaluated the capacity of multiple modalities to detect these alterations, including loss of heterozygosity (LOH), fluorescence in situ hybridization (FISH), and comparative genomic hybridization (CGH). The correlation coefficients for detection of 1p and 19q alterations, respectively, between modalities were: 0.98 and 0.87 for LOH and FISH, 0.79 and 0.60 for LOH and CGH, and 0.79 and 0.53 for FISH and CGH. Minimal deletion regions were defined on 19q13.3 (D19S412-D19S596) and 1p (D1S468-D1S1612). Loss of the 1p36 region was found in 18% of astrocytomas (10/55) and in 73% (24/33) of oligodendrogliomas (P < 0.0001), and loss of the 19q13.3 region was found in 38% (21/55) of astrocytomas and 73% (24/33) of oligodendrogliomas (P = 0.0017). Loss of both regions was found in 11% (6/55) of astrocytomas and in 64% (21/33) of oligodendrogliomas (P < 0.0001). All gliomas with LOH on either 1p or 19q demonstrated loss of the corresponding FISH probe, 1p36 or 19q13.3, suggesting not only locations of putative tumor suppressor genes, but also a simple assay for assessment of 1p and 19q alterations as diagnostic and prognostic markers.

Astrocytoma↗
PubMed1999

"Malignancy" in meningiomas: a clinicopathologic study of 116 patients, with grading implications.

BACKGROUND: Due to the rarity of malignancy in meningiomas, prior studies have been limited to small series. Controversies regarding the definition of malignant meningioma have complicated matters further. Although histologic anaplasia and extracranial metastasis are established criteria, the former is difficult to define and the latter represents a clinical finding. Traditionally, brain invasion has also been accepted, although this has recently been debated. In a prior series, the authors were unable to prove that 23 meningiomas that had invaded the brain were more aggressive than atypical meningiomas. METHODS: The authors expanded their analysis to include 116 patients diagnosed with "malignant meningioma" due to brain invasion, frank anaplasia (20 mitoses per 10 high-power fields or histology resembling carcinoma, sarcoma, or melanoma), and/or extracranial metastasis. Patients were followed until death or for a median of 3.7 years. RESULTS: Survival time was highly variable, ranging from 10 days to 24 years. In multivariate analysis, histologic anaplasia (P=0.0035), subtotal resection (P=0.0038), 20 mitoses per 10 high-power fields (P=0.0071), and nuclear atypia (P=0.0068) were associated with poor survival. Of the 89 cases of meningioma that had invaded the brain, 23% were otherwise benign, 61% were otherwise atypical, and 17% were frankly anaplastic. Those without anaplasia behaved similarly to atypical meningiomas from the authors' prior study. In contrast, anaplastic meningiomas were usually fatal, associated with a median survival of 1.5 years. CONCLUSIONS: Based on these findings, the authors suggest that brain invasion constitutes an additional criterion for the diagnosis of atypical meningioma (World Health Organization [WHO] Grade II), whereas frank anaplasia indicates high grade (WHO Grade III-IV) malignancy.

Adolescent↗
PubMed1999

Randomised controlled trial of efficacy of teaching patients with bipolar disorder to identify early symptoms of relapse and obtain treatment.

OBJECTIVE: To determine the efficacy of teaching patients with bipolar disorder (manic-depressive psychosis) to identify early symptoms of relapse and seek prompt treatment from health services. DESIGN: Single blind randomised controlled trial with matching on four baseline variables using a minimisation algorithm. SETTING: Mental health services in four NHS trusts (one teaching, three non-teaching). SUBJECTS: 69 patients with bipolar disorder who had had a relapse in the previous 12 months. INTERVENTIONS: Seven to 12 individual treatment sessions from a research psychologist plus routine care or routine care alone. MAIN OUTCOME MEASURES: Time to first manic or depressive relapse, number of manic or depressive relapses, and social functioning examined by standardised interviews every six months for 18 months. RESULTS: 25th centile time to first manic relapse in experimental group was 65 weeks compared with 17 weeks in the control group. Event curves of time to first manic relapse significantly differed between experimental and control groups (log rank 7.04, df=1, P=0.008), with significant reductions in the number of manic relapses over 18 months (median difference 30% (95% confidence interval 8% to 52%), P=0.013). The experimental treatment had no effect on time to first relapse or number of relapses with depression, but it significantly improved overall social functioning (mean difference 2.0 (0.7 to 3.2), P=0.003) and employment (mean difference 0.7 (0.1 to 1.3), P=0.030) by 18 months. CONCLUSION: Teaching patients to recognise early symptoms of manic relapse and seek early treatment is associated with important clinical improvements in time to first manic relapse, social functioning, and employment.

Adolescent↗
PubMed1999

Expression of TGFalpha in meningiomas.

The objective of this study was to examine the expression of transforming growth factor alpha (TGFalpha), a mitogen for many cell types, and its receptor in basic subtypes of meningiomas as well as in meningiomas of varying grade. Formalin-fixed tissues from 26 meningiomas including 15 benign (5 meningothelial, 5 transitional, and 5 fibrous variants), 6 atypical, and 5 malignant examples were immunohistochemically examined for both TGFalpha protein and EGF/TGFalpha receptor protein. In addition, in situ hybridization (ISH) was used to detect TGFalpha mRNA expression. Immunostaining for TGFalpha was strongest in fibrous and atypical meningiomas, followed closely by transitional and malignant tumors. Only weak reactivity was observed in the meningothelial variant. In all but 4 tumors (2 fibrous, 2 atypical), ISH showed TGFalpha mRNA to be present, the signal being stronger in malignant than in conventional or atypical tumors. Lastly, immunostaining for EGF/TGFalpha receptor was positive in all tumors studied. Strong TGFalpha protein expression in meningiomas is commonly associated with fibrous morphology. Although the frequent detection of both TGFalpha protein and its mRNA, as well as of EGF/TGFalpha receptor within tumors of all type and grades, suggests that TGFalpha serves to promote tumor growth, its possible role in tumorigenesis or malignant progression is uncertain. In summary, demonstration of these substances is of no utility in the classification or grading of this common tumor because the differences in their expression among the various meningioma subtypes were not statistically significant.

Adult↗
PubMed1999

Early PCR-negativity after allogeneic BMT in adults with t(4;11) ALL in the absence of acute or chronic GVHD.

Acute lymphoblastic leukaemia (ALL) with the t(4;11) translocation has a very poor prognosis following conventional chemotherapy. Many patients are offered an allogeneic BMT in first remission. We report on the impact of allogeneic BMT on three patients with t(4;11) ALL in first remission. Median age was 20 years. One patient received marrow from an HLA-identical sibling and the other two from unrelated donors. All three engrafted and none of the patients developed acute or chronic GVHD. Remission status was monitored using a sensitive nested RT-PCR to detect the ALL-1/AF-4 hybrid transcript. All three were PCR-negative at 3 months post-BMT. One of the unrelated recipients died of a fungal infection 4 months post-BMT. The other two are alive and in molecular remission at 21 and 24 months post-BMT. This is the first report of longitudinal follow-up of t(4;11) ALL post-allogeneic BMT by PCR. The early attainment of molecular remission in the absence of GVHD suggests that the conditioning regimen may have been more important than a graft-versus-leukaemia effect in these patients. Follow-up of larger numbers of patients will be required to confirm these preliminary observations.

Acute Disease↗
PubMed1999

Detection of p16, RB, CDK4, and p53 gene deletion and amplification by fluorescence in situ hybridization in 96 gliomas.

Inactivation of the p53 gene is a common early event of astrocytoma tumorigenesis. Alternatively, since the p16, retinoblastoma (RB), and CDK4 genes have been implicated in malignant progression, detection of losses or amplifications of these genes in gliomas could be diagnostically, prognostically, and therapeutically important. We obtained smear preparations from 96 diffuse gliomas and 10 nonneoplastic specimens. Dual-color fluorescence in situ hybridizations using paired probes for CEN9/p16, CEN8/RB, CEN17/p53, and CEN12/CDK4 were performed and revealed expected frequencies of abnormalities, except for p53 losses, which were low (7%). The latter supports the concept that p53 inactivation usually occurs by mitotic recombination. Detected abnormalities of the p16/RB/CDK4 pathway were highly associated with astrocytic differentiation and were univariately associated with decreased patient survival. However, only patient age and histologic classification retained statistical significance on multivariate analysis. We conclude that in diffuse gliomas, p16/RB/CDK4 abnormalities are markers of astrocytic phenotype. Thus, their detection by fluorescence in situ hybridization may have diagnostic usefulness in cases with equivocal morphologic features. Although our numbers are small, we find no additional prognostic significance to these genetic abnormalities one age, grade, and oligodendroglial histology are taken into account.

Adult↗
PubMed1999

Cardiopulmonary and CD4 cell changes in response to exercise training in early symptomatic HIV infection.

PURPOSE: The purposes of the present study were to assess the effects of a 12-wk laboratory based aerobic exercise program on cardiopulmonary function, CD4 cell count, and physician-assessed health status among symptomatic pre-AIDS HIV-infected individuals (N = 28) and to assess the degree to which ill health was associated with exercise relapse. METHODS: Responses to graded exercise test, physician-assessed health status, and CD4 cell counts were determined at baseline and 12-wk follow-up for participants randomly assigned to exercise or control conditions, and reasons for exercise noncompliance were recorded. RESULTS: Approximately 61% of exercise-assigned participants complied (> 50% attendance) with the exercise program, and analyses of exercise relapse data indicated that obesity and smoking status, but not exercise-associated illness, differentiated compliant from noncompliant exercisers. Compliant exercisers significantly improved peak oxygen consumption (VO2peak; 12%), oxygen pulse (O2pulse; 13%), tidal volume (TV; 8%), ventilation (VE; 17%), and leg power (25%) to a greater degree than control participants and noncompliant exercisers (all P < 0.05). Although no group differences in health status were found, a significant interaction effect indicated that noncompliant exercisers' CD4 cells declined (18%) significantly, whereas compliant exercisers' cell counts significantly increased (13%; P < 0.05). CONCLUSION: We conclude that although aerobic exercise can improve cardiopulmonary functioning in symptomatic HIV-infected individuals with minimal health risks, attention to factors associated with exercise adherence is warranted.

Adult↗
PubMed1999

Aggressive enterogenous cyst with extensive craniospinal spread: case report.

OBJECTIVE AND IMPORTANCE: Considered benign and malformative in nature, enterogenous cysts are predominantly spinal lesions. Although recurrences have been reported, especially in the rare intracranial examples, craniospinal dissemination has never been described. CLINICAL PRESENTATION: We report a 63-year-old woman who presented 16 years previously with a histologically typical enterogenous cyst of the cerebellum. Fourteen years after its incomplete excision, numerous supratentorial, infratentorial, and spinal subarachnoid cysts were detected. A histological examination revealed multiple enterogenous cysts without evidence of malignancy. Ki-67 (MIB-1) proliferative indices were less than 1% in all except one specimen, wherein it was 4%; immunohistochemistry demonstrated rare p53 protein overexpression. INTERVENTION: During the last 2 years, four subtotal resections of spinal enterogenous cysts have been performed for progressive paraplegia, pain, paresthesia, and bladder dysfunction. Considering the multiple recurrences and progressive neurological deficits, craniospinal radiation therapy was given. CONCLUSION: To our knowledge, this is the first report of widespread craniospinal dissemination associated with the incomplete resection of an enterogenous cyst. Although a rare complication, it emphasizes the advantages of early, aggressive surgery.

Bone Diseases↗
PubMed1999

The influence of training on tinnitus perception: an evaluation 12 months after tinnitus management training.

Sixty-five subjects were reviewed 12 months after tinnitus management training, which had been comprised variously of information, relaxation training and a therapeutic noise strategy. Seventy-four per cent of subjects reported increased habituation to tinnitus (n = 48), 65% reported reduced tinnitus annoyance (n = 42), and 52% reported an increased ability to cope with tinnitus (n = 34). Twenty-five per cent of subjects reported deterioration in coping ability (n = 16), 23% reported reduced habituation to tinnitus (n = 15) and 8% reported increased tinnitus-related annoyance (n = 5). None of the management strategies were found to be significantly more effective than others in facilitating improved coping or habituation to tinnitus. Subjects who reported reduced coping and habituation to tinnitus experienced greater levels of general life stress than subjects who reported increased habituation and coping ability. The use of relaxation therapies as applied in this study did not appear to influence the level of tinnitus distress or the level of life stress. Thirty-seven per cent of subjects given long-term low-level white noise (LTWN) stimulation reported benefit. However, LTWN stimulation did not significantly alter tinnitus awareness or the minimum masking level (MML) of tinnitus. Long-term low-level white noise stimulation appeared to influence cognitive reaction to tinnitus rather than its physical perception. Subjects who initially had low ability to cope with tinnitus and preferred a more active coping style reported significantly greater benefit from LTWN stimulation than subjects whose primary approach to coping was to regulate the emotional impact of tinnitus.

Adaptation, Psychological↗
PubMed1999

Meningioma metastatic to the lung.

Meningiomas constitute 15% to 18% of all primary intracranial and intraspinal tumors. Distant extracranial metastases are reported to occur in fewer than 1 in 1000 cases. Of 1992 primary intracranial meningiomas seen at Mayo Clinic Rochester from 1972 through 1994, we identified 3 (0.15%) with documented extracranial metastasis. A review of the literature suggests that previous craniotomy, venous sinus invasion, local recurrences, histological malignancy, and papillary morphology may be risk factors for systemic spread, as demonstrated in our cases. Although rare, metastatic meningioma should be considered in the differential diagnosis of abnormal findings on chest radiography in patients with known or suspected intracranial meningioma.

Adolescent↗
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↗