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P Molloy

Publications and source records attributed to P Molloy.

16 recordsLinked to original sources

Dynamic modelling of prosthetic chorded mitral valves using the immersed boundary method.

Current artificial heart valves either have limited lifespan or require the recipient to be on permanent anticoagulation therapy. In this paper, effort is made to assess a newly developed bileaflet valve prosthesis made of synthetic flexible leaflet materials, whose geometry and material properties are based on those of the native mitral valve, with a view to providing superior options for mitral valve replacement. Computational analysis is employed to evaluate the geometric and material design of the valve, by investigation of its mechanical behaviour and unsteady flow characteristics. The immersed boundary (IB) method is used for the dynamic modelling of the large deformation of the valve leaflets and the fluid-structure interactions. The IB simulation is first validated for the aortic prosthesis subjected to a hydrostatic loading. The predicted displacement fields by IB are compared with those obtained using ANSYS, as well as with experimental measurements. Good quantitative agreement is obtained. Moreover, known failure regions of aortic prostheses are identified. The dynamic behaviour of the valve designs is then simulated under four physiological pulsatile flows. Experimental pressure gradients for opening and closure of the valves are in good agreement with IB predictions for all flow rates for both aortic and mitral designs. Importantly, the simulations predicted improved physiological haemodynamics for the novel mitral design. Limitation of the current IB model is also discussed. We conclude that the IB model can be developed to be an extremely effective dynamic simulation tool to aid prosthesis design.

Biocompatible Materials↗

A new physician's guide to evaluating managed care opportunities.

AUDIENCE: This article is designed for new physicians and administrators who evaluate and negotiate as providers with managed care organizations. GOALS: To provide a review of the major issues impacting on medical practices as they develop contractual relationships with managed care organizations. OBJECTIVES: 1. To review the four major types of health maintenance organizations, providing some general detail about the financial policies of each. 2. To outline how utilization review and quality assurance policies can affect individual physician practice. 3. To discuss risk-sharing arrangements employed by managed care organizations, including their financial and clinical impact, and to outline the issues a new physician should consider when evaluating a contract.

Capitation Fee↗

Adjuvant chemotherapy for the treatment of intracranial ependymoma of childhood.

BACKGROUND: Current treatment for childhood intracranial ependymomas with surgery and radiation therapy (RT) yields 5-year survival rates ranging from 50-70% after complete resection to 0-30% after incomplete surgical resection. The role of chemotherapy in the treatment of ependymoma has not been established. In this pilot study, children with newly diagnosed intracranial ependymoma were treated with RT and chemotherapy using agents comparable to those found to be active in the treatment of intracranial ependymoma in infants. METHODS: Nineteen children age 3-14 years (median, 7.5 years) were treated with postoperative RT and chemotherapy. Chemotherapy was comprised of carboplatin, 560 mg/m2, with vincristine, 1.5 mg/m2, weekly for 3 weeks, alternating at 4-week intervals with ifosfamide, 1.8 g/m2, and etoposide, 100 mg/m2, for 5 consecutive days for a total of 4 cycles. RESULTS: The 5-year progression free survival (PFS) estimate was 74%. The extent of surgical resection was not a significant prognostic factor in this study. By contrast, ependymomas located in the posterior fossa were associated with a higher rate of progression (P = 0.036). Toxicity, limited predominantly to myelosuppression, was manageable. CONCLUSIONS: The PFS for children with postoperative residual ependymoma treated with RT and chemotherapy in this study was higher than published survival results for RT alone. These results suggest a role for multialkylator chemotherapy in incompletely resected intracranial ependymoma and provide the rationale for a randomized trial comparing this strategy with conventional postoperative RT.

Adolescent↗

Endocrine outcome in long-term survivors of low-grade hypothalamic/chiasmatic glioma.

OBJECTIVE: We have evaluated the frequency of endocrine abnormalities in a large group of patients with hypothalamic/chiasmatic glioma (H/CG) and its correlation with the different forms of therapy. DESIGN: Descriptive retrospective study using case note review analysis. PATIENTS: The records of 68 children who survived H/CG were analysed. One third had neurofibromatosis. The mean age at tumour presentation was 5 years. The median time of follow-up was 3.6 years. Thirty-eight children received cranial radiation, of whom 17 also had surgery. Surgery was performed in a total of 24 patients. Fifteen patients received only chemotherapy. Eight children, all with neurofibromatosis, received no specific tumour treatment. MEASUREMENTS: Endocrine dysfunction was determined by clinical manifestations and biochemical evaluation of hypothalamic-pituitary function. RESULTS: Endocrine dysfunction occurred in 42% of the children. The most common disorder was GH deficiency (GHD). Of 50 children evaluated, 15 of the 19 with GHD received cranial irradiation (P < 0.05). HOwever, 15 children treated with more than 15 Gy grew normally. Precocious puberty was diagnosed in 11 patients. Nine patients, all treated with cranial irradiation, developed hypogonadotrophic hypogonadism. Of the 14 patients with hypothyroidism, 10 had surgery (P < 0.005). Hypoadrenalism and diabetes insipidus each occurred in eight patients, and were associated with multiple endocrine deficiencies and surgery. Endocrine deficiencies occurred in children with neurofibromatosis as frequently as children without neurofibromatosis but only when comparing those treated with cranial irradiation or surgery. CONCLUSIONS: Nearly all studies assessing the patients with different tumour therapy evaluate patients wit different tumour types. This study investigates a specific and large population of patients with H/CG and correlates the different form of treatment with the endocrine outcome. Precocious puberty, in children with this tumour, is probably due to tumour location rather than oncological therapy. Conversely, although endocrine deficiencies can be a result of tumour location, the major causes of endocrine abnormalities were field irradiation and tumour surgery. A notable finding not previously reported is that endocrine dysfunction occurs less often in neurofibromatosis patients treated conservatively. Furthermore, this study documents that a significant number of young children grew normally despite receiving brain irradiation of greater than 45 Gy.

Adolescent↗

Proton spectroscopy of suprasellar tumors in pediatric patients.

OBJECTIVE: Magnetic resonance imaging and computed tomography provide good anatomic detail of suprasellar tumors in pediatric patients but are not able to predict histology in many cases. Proton magnetic resonance spectroscopy provides metabolic data that may add to diagnostic specificity. We preoperatively performed localized proton magnetic resonance spectroscopy on pediatric patients with suprasellar tumors and correlated the results with the histological findings. Cyst fluid obtained from patients with craniopharyngiomas was studied with high-resolution magnetic resonance spectroscopy to better understand the in vivo data. METHODS: Nineteen patients aged 1 to 21 years underwent spectroscopy. Surgical pathological samples were obtained from 14 patients. In each of five patients, the presence of a solid chiasmatic mass in addition to clinical evidence of neurofibromatosis Type I allowed the presumptive diagnosis of chiasmatic astrocytoma. Thus, the study population included 6 patients with craniopharyngiomas, 10 with chiasmatic/hypothalamic astrocytomas, and 3 with pituitary adenomas. The data obtained were compared with those of healthy brain from age-matched participants. RESULTS: Spectroscopy was specific for the diagnosis. All craniopharyngiomas showed a dominant peak at 1 to 2 ppm, consistent with lactate or lipids, with trace amounts of other metabolites. This was confirmed using high-resolution spectroscopy. Chiasmatic gliomas showed a profile of choline, N-acetylaspartate, and creatine, and the choline:N-acetylaspartate ratio was 2.6 +/- 1.3, compared with 0.7 +/- 0.3 for samples of healthy brain (t test, P = 0.0003). Pituitary adenomas showed only a choline peak or no metabolites at all. CONCLUSION: Proton spectroscopy may be helpful in supplementing standard imaging for the preoperative diagnosis of three types of suprasellar tumors that are common in pediatric patients.

Adenoma↗

Clinical outcome of pediatric gangliogliomas: ninety-nine cases over 20 years.

Gangliogliomas account for 1-4% of all pediatric CNS tumors. We reviewed the records of 123 patients treated at the Children's Hospital of Philadelphia between 1974 and 1995. Ninety-nine patients were eligible for review with complete medical records. The mean age was 9.5 years with 52% females. The mean follow-up was 3.7 years. The most common presenting symptom was seizures (49%). The mean length of symptoms to diagnosis was 24.4 months. Complex partial seizure was the most frequent seizure type (60%). Electroencephalograms were abnormal in 36%. The majority of gangliogliomas were in the temporal lobes (38%), with other sites in the parietal (30%) and frontal lobes (18%). All patients had abnormal nonspecific neuroimaging studies. Nine received chemotherapy, and 21 were treated with radiotherapy. Postoperatively, 78% were seizure free on no medication, 18% had improvement of seizure control, and 4% had stable seizure events. Nine died of disease. Gangliogliomas are benign tumors that frequently present with seizure disorders and nonspecific electroencephalographic and neuroimaging studies. Complete surgical extirpation of these tumors provides improved seizure control in most patients and a short course of antiepileptic medical therapy. Adjuvant therapy including radiotherapy and chemotherapy is limited to recurrent disease not amenable to reoperation.

Adolescent↗

Postoperative surveillance imaging in children with cerebellar astrocytomas.

The standard follow-up care for children with cerebellar astrocytomas includes regular surveillance imaging of the brain with computerized tomography or magnetic resonance. The purpose of surveillance imaging is to detect asymptomatic tumor recurrence at an early stage and permit safer reoperation. The authors evaluated the effectiveness of an intensive surveillance program for cerebellar astrocytoma and tested different models of surveillance frequency and duration to arrive at a specific recommended program. Review of the records of 93 children with typical cerebellar astrocytomas who received follow-up care between 1975 and 1993 was performed. Immediate postoperative and surveillance images were classified as showing definite equivocal, or no tumor based on the radiology report at the time the image was obtained. Various surveillance models were then tested for their predictive value for detecting tumor recurrence. Seventeen (18%) of the 93 children had tumor recurrence or progression. Eleven of these tumors were asymptomatic and detected only by surveillance image. Tumor recurred in only one patient with a total resection, whereas tumor progression occurred in five of 21 patients with equivocal postoperative images and in 11 of 14 patients with residual tumor. A model in which patients with possible or definite residual tumor after surgery undergo surveillance at 12, 18, 30, 42, and 66 months, and later have one additional image, yielded optimum predictive value for recurrence and/or progression with the fewest images. Patients with tumor recurrence were satisfactorily treated, and only one patient died. Children with totally resected cerebellar astrocytomas do not appear to benefit from routine surveillance, because the likelihood of recurrence is small. Surveillance is of benefit in those who may have subtotal resection based on the immediate postoperative imaging.

Astrocytoma↗

Separation and concentration of bacteria with immobilized antibody fragments.

New methods to quantitatively remove bacteria from food and water samples are required to meet modern safety standards. The recent development of techniques to make Fab/Fv/scFv fragments in bacteria has provided the opportunity to exploit antibodies as specialized chemicals for affinity removal technologies. Single-chain fragments against Pseudomonas aeruginosa have been expressed in Escherichia coli, purified via a fused poly-histidine tail and immobilized upon polystyrene beads. The resulting immunoaffinity columns have been shown to effectively remove greater than 90% of an applied 10 million bacteria after a single passage through the column. Column material in the absence of single-chain retained less than 10% of the bacteria. Pseudomonas were also removed from milk, mixed bacterial cultures and when present at low cell densities.

Antibodies, Bacterial↗

SSCP detection of N-ras promoter mutations in AML patients.

Activation of the N-ras gene via coding region mutations has been previously documented in 25% of patients with acute myeloid leukemia (AML). Since overexpression of normal N-ras is also transforming in vitro, the N-ras promoter of AML patients was analyzed for the presence of promoter mutations that may affect expression of the N-ras gene. Single-stranded conformational polymorphism (SSCP) was used to analyze samples from 26 AML patients and 13 normal subjects. A novel polymorphism at position 390 within the N-ras promoter was observed in both AML patients and normal samples at an overall frequency of 26%. In addition, two of 26 patients had single-base substitutions within protein binding sites that altered the binding of transcription factors to the promoter. One patient had a T-->A mutation at position 520 within an AP-1 binding site; the other had an A-->G mutation at position 409 within a protein binding region adjacent to a Myb binding site. The data suggest that in addition to coding region mutations in the N-ras gene, mutations in the promoter region that could alter regulation of N-ras expression provide an alternative mechanism of involvement of N-ras in AML.

Base Sequence↗

The Oklahoma-Pittsburgh experience with interferon alpha in the treatment of HCV disease.

Interferon alpha (IFN) is the only Food and Drug Administration (FDA)-approved therapy available for the treatment of chronic hepatitis C. The ideal dose and frequency of IFN administration that produces the greatest number of patient responders with the least number of relapses following drug withdrawal remains unclear. METHODS. One hundred seventeen patients recruited over a five-year period with chronic hepatitis C were divided into four groups and treated with progressively larger doses. The rate of clinical responses defined as a loss of detectable hepatitis C virus-ribonucleic acid (HCV-RNA) in serum by polymerase chain reaction (PCR) and normalization of the serum ALT (abnormal alanine aminotransferase) for each group was calculated. RESULTS. As the dose of IFN administration increased, the response rate defined by the absence of HCV-RNA in the patient's serum after six months of follow-up increased from 7.7% to 26.6%. If the end point utilized was HCV-RNA negativity after six months of treatment, the response rate varied from 19.2% to 30%. Using the less difficult end point of a normal ALT level, the response rates varied from 32.1% to 63.3% after six months of therapy and from 10.7% to 26.7% after six months of follow-up. CONCLUSIONS. This experience demonstrates that both the response rate at the end of therapy and after six months of follow-up improves with an increase in dose of IFN administered over a six-month period.

Adult↗

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Educational Measurement↗

The relationship between risk factors for affective disorder and poststroke depression in hospitalised stroke patients.

The influence of psychiatric risk factors on the development of depression following stroke was examined in 88 patients undergoing inpatient rehabilitation. In this sample, 34 patients (38%) had a diagnosis of major or minor depression. Older age and a personal or family history of affective or anxiety disorder were associated significantly with major depression. Minor depression was more common among males and those patients with greater physical disability. Severity of depressive symptoms was associated with a personal or family history of affective or anxiety disorder and higher pre-stroke personality neuroticism. We conclude that certain psychiatric risk factors for affective disorder are strongly associated with poststroke depression. The implications of these findings for anticipating and managing poststroke depression are discussed.

Adaptation, Psychological↗