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Biomedical subjects

M Cusimano

Publications and source records attributed to M Cusimano.

17 recordsLinked to original sources
PubMed2006

Dendritic cells pulsed with glioma lysates induce immunity against syngeneic intracranial gliomas and increase survival of tumor-bearing mice.

In recent years, the use of dendritic cells (DC), the most powerful antigen presenting cells, has been proposed for the creation of vaccines against gliomas. This approach has been demonstrated to be safe and non-toxic in phase I or I-II trials (2, 3). Immunotherapy plays a central role in the search for new treatments for glioblastoma multiforme (GBM). In particular, several phase I studies have been performed using DC pulsed by GBM proteins as a vaccine for patients with relapsing GBM. The studies demonstrated that DC vaccination is safe and may produce a significant increase in overall survival. As the first step in the preparation of appropriate conditions for a clinical evaluation in Italy, we have performed pre-clinical experiments on immune-competent mice injected intra-cerebrally with syngeneic GL261GBM cells and treated subcutaneously and intra-tumorally with DC loaded with a GL261 homogenate. These results show that vaccination with DC pulsed with a tumor lysate increases considerably survival in mice bearing intracranial glioblastomas and supports the development of DC-based clinical trials for patients with glioblastomas that do not respond to standard therapies.

Animals↗
PubMed2005

Prognostic indicators in an aggressive pituitary Crooke's cell adenoma.

OBJECTIVE: To investigate prognostic indicators in an aggressive Crooke's cell adenoma of the pituitary. METHODS: The surgically removed tumor was studied by histology, immunohistochemistry and transmission electron microscopy. RESULTS: An aggressive invasive sellar tumor removed by repeated surgeries from a 43-year-old woman with pituitary related Cushing's disease was classified as a Crooke's cell adenoma of the pituitary. The application of several cell proliferation markers confirmed the aggressive nature of the tumor. CONCLUSIONS: The investigation of the present case provides additional evidence that pituitary Crooke's cell adenomas may possess aggressive behavior.

Adenoma↗
PubMed2001

Setting performance standards for medical practice: a theoretical framework.

BACKGROUND: The assessment of performance in the real world of medical practice is now widely accepted as the goal of assessment at the postgraduate level. This is largely a validity issue, as it is recognised that tests of knowledge and in clinical simulations cannot on their own really measure how medical practitioners function in the broader health care system. However, the development of standards for performance-based assessment is not as well understood as in competency assessment, where simulations can more readily reflect narrower issues of knowledge and skills. This paper proposes a theoretical framework for the development of standards that reflect the more complex world in which experienced medical practitioners work. METHODS: The paper reflects the combined experiences of a group of education researchers and the results of literature searches that included identifying current health system data sources that might contribute information to the measurement of standards. CONCLUSION: Standards that reflect the complexity of medical practice may best be developed through an "expert systems" analysis of clinical conditions for which desired health care outcomes reflect the contribution of several health professionals within a complex, three-dimensional, contextual model. Examples of the model are provided, but further work is needed to test validity and measurability.

Clinical Competence↗
PubMed2001

Assessment of English proficiency in international medical graduates by physician examiners and standardized patients.

CONTEXT: Since 1986, the Ontario Ministry of Health has provided a medical licensure preparation programme for international medical graduates. Because of the diversity in candidates' oral English proficiency, this competency has been viewed as a particularly important selection criterion. OBJECTIVES: To assess and compare the quality of ratings of oral English proficiency of international medical graduates provided by physician examiners and by standardized patients (SPs). PARTICIPANTS AND MATERIALS: The study samples consisted of 73 candidates for the Ontario International Medical Graduate (IMG) Program, and physician examiners and SPs in five 10-minute encounter objective structured clinical examination (OSCE) stations. Materials used were a seven-item speaking performance rating instrument prepared for the Ontario IMG Program. METHODS: Rating sheets were scanned and the results analysed using SPSS 9.0 for Windows. RESULTS: Correlations between the physician and SP ratings on the seven items ranged from 0.52 to 0.70. The SPs provided more lenient ratings. Mean alpha reliability for the physicians' ratings on the seven items was 0.59, and for the SPs' 0.64. There was poor agreement between the two sets of raters in identifying problematic candidates. CONCLUSIONS: Notwithstanding the sizable correlations between the ratings provided by the two rater groups, the results demonstrated that there was little agreement between the two groups in identifying the potentially problematic candidates. The physicians were less prone than the SPs to rate candidates as problematic. SPs may be better placed than the physician examiners to directly assess IMG candidates' oral English proficiency.

Educational Measurement↗
PubMed2001

A method to estimate urinary electrolyte excretion in patients at risk for developing cerebral salt wasting.

OBJECT: Two major criteria are necessary to diagnose cerebral salt wasting (CSW): a cerebral lesion and a large urinary excretion of Na+ and Cl- at a time when the extracellular fluid (ECF) volume is contracted. Nevertheless, it is difficult for the physician to confirm from bedside observation that a patient has a contracted ECF volume. Hyponatremia, although frequently present, should not be a criterion for a diagnosis of salt wasting. A contracted ECF volume is unlikely if there are positive balances of Na+ and Cl-. The goal of this study was to assess the accuracy of calculating balances for Na+ plus K+ and of Cl- over 1 to 10 days in an intensive care unit (ICU) setting. METHODS: A prospective comparison of measured and estimated quantities of Na+ plus K+ and of Cl- excreted over 1 to 10 days in 10 children and 12 adults who had recently received a traumatic brain injury or undergone recent neurosurgery. Plasma concentrations of electrolytes were recorded at the beginning and end of the study period. The total volumes infused and excreted and the concentrations of Na+, K+, and Cl- in the infusate were obtained from each patient's ICU chart. The electrolytes in the patients' urine were measured and calculated. Correlations between measured and calculated values for excretions of Cl- and of Na+ plus K+ were excellent. CONCLUSIONS: Mass balances for Na+ plus K+ and for Cl- can be accurately estimated. These data provide information to support or refute a clinical diagnosis of CSW. The danger of relying on balances for these electrolytes measured within a single day to diagnose CSW is illustrated.

Adolescent↗
PubMed2000

A comparison of physician examiners', standardized patients', and communication experts' ratings of international medical graduates' English proficiency.

PURPOSE: To assess the quality of ratings of interviewing skills and oral English proficiency provided on a clinical skills OSCE by physician examiners, standardized patients (SPs), and communication skills experts. METHOD: In 1998, 73 candidates to the Ontario International Medical Graduate (OIMG) Program completed a 29-station OSCE-type clinical skills selection examination. Physician examiners, SPs, and communication skills experts assessed components of oral English proficiency and interview performance. Based on these results, the frequency and generalizability of English-language flags, physician examiners' indications that spoken English skills were bad enough to significantly impede communication with patients; the reliability of the OIMG's Interview and Oral Performance Scales and generalizability of overall interview and oral performance ratings; and comparisons of repeated assessments by experts were calculated. Principal-components analysis was applied to the panels' ratings to determine a more economical expression of the language proficiency and interview communication skills results. RESULTS: The mean number of English-language flags per candidate was 2.1, the median was 1.0, and Cronbach's alpha of the ratings was 0.63. Means, SDs, and alphas of the physician examiners' and SPs' ratings of the interview performance scale were 9.15/10, 0.43, 0.36, and 9.30/10, 0. 56, 0.50, respectively. Corresponding values for overall interview performance ratings were 3.08/4, 0.30, 0.33, and 3.34/4, 0.32, 0.47. Means, SDs, and alphas of the physician examiners' and SPs' ratings of the oral performance scale were 8.54/10, 0.74, 0.78, and 8.74/10, 1.00, 0.76. Corresponding values for overall ratings of oral performance were 3.85/5, 0.51, 0.68, and 4.08/5, 0.60, 0.68. For the two experts' ratings of two contiguous five-minute interview stations, internal consistencies were 0.88 and 0.78. For the two experts' ratings of standardized ten-minute interviews, internal consistencies were 0.81 and 0.92. Correlations between the mean values of the experts' ratings of the ten- and five-minute stations were 0.45 and 0.51. Three factors emerged from the PCA, language proficiency, physician examiners' ratings of interview proficiency, and SPs' ratings of interview proficiency. CONCLUSIONS: Consistency between the physician examiners' and SPs' ratings of English proficiency was observed; less agreement was observed in their ratings of interviewing skills, and little agreement was observed between the experts' ratings. Communication skills results may be validly expressed by three measures: one overall global rating of language proficiency provided by physician examiners or SPs, and overall global ratings of interview proficiency provided separately by physician examiners and SPs.

Clinical Competence↗
PubMed1999

Assessment of technical skills transfer from the bench training model to the human model.

BACKGROUND: This study examines whether technical skills learned on a bench model are transferable to the human cadaver model. METHODS: Twenty-three first-year residents were randomly assigned to three groups receiving teaching on six procedures. For each procedure, one group received training on a cadaver model, one received training on a bench model, and one learned independently from a prepared text. Following training, all residents were assessed on their ability to perform the six procedures. RESULTS: Repeated measures analysis of variance revealed a significant effect of training modality for both checklist scores (F(2,44) = 3.49, P <0.05) and global scores (F(2,44) = 7.48, P <0.01). Post-hoc tests indicated that both bench and cadaver training were superior to text learning and that bench and cadaver training were equivalent. CONCLUSIONS: Training on a bench model transfers well to the human model, suggesting strong potential for transfer to the operating room.

Cadaver↗
PubMed1999

Cytology of pituitary thyrotroph hyperplasia in protracted primary hypothyroidism.

Pituitary thyrotroph hyperplasia, a rare cause of pituitary enlargement, is usually associated with protracted primary hypothyroidism. We present here a case of pituitary thyrotroph hyperplasia in a 51 year old woman who was thought to have a pituitary macroadenoma with suprasellar extension. The cytologic investigation of the intraoperative touch preparation identified hyperplastic thyrotrophs, provided the correct diagnosis and helped to limit further aggressive surgical removal of the lesion, which is known to regress after adequate thyroid hormone replacement therapy. This is the first study to describe the cytologic features of pituitary thyrotroph hyperplasia confirmed subsequently by histology, immunocytochemistry and transmission electron microscopy.

Adenoma↗
PubMed1998

Utility of frameless stereotaxy in the resection of skull base and Basal cerebral lesions in children.

Since 1991, we have performed nearly 300 stereotactic procedures using the ISG viewing wand on a variety of cranial lesions in patients under 22 years of age. Of these, 38 procedures were performed on 34 patients for basal cerebral and skull base lesions. Our patients ranged in age from 3.5 months to 22 years with a mean age of 9.45 years. There were 18 females and 16 males. Twenty-one patients had basal cerebral lesions located in the thalamus (10), basal ganglia (2), third ventricle (2), and hypothalamus (7). Thirteen patients had skull base lesions located within the anterior optic apparatus (3), sella turcica (4), middle and posterior cranial fossae (4), and craniocervical region (2). Preoperative CT and/or MRI scan images were taken as a volume acquisition and transferred to the computer workstation utilizing the ISG Wand software. This workstation was transferred to the operating room where it was calibrated to a faro Surgicom arm which interfaces with the patient and the three-dimensional radiological image. The ISG Wand was utilized to plan the scalp and bone flaps and to select the optional trajectory to lesion. The surgical approaches which were specifically used in this series with the ISG Wand included transcallosal (15), pterional (5), frontal (3), subtemporal (4), transsphenoidal (3), temporal (3), tumor cyst shunt insertion (1), burr hole drainage (1), transoral (2), bifrontal (1), bifrontal mid facial (1), and transnasal (1). Although brain shift occurred following craniotomy and with brain retraction, the relative immobility of these lesions at the skull or cerebral base permitted an accurate targeting of all lesions with an error range of 1.0-2.5 mm throughout the entire procedure. This relatively precise intraoperative feedback led to more accurate recognition of tumor landmarks. It is the authors' impression that a more aggressive resection of these lesions was achieved than could be without the device. We conclude that a frameless stereotactic device such as the ISG Wand is particularly valuable in the approach to skull base and basal cerebral tumors in children.

Journal Article↗
PubMed1996

Surgical treatment of meningiomas involving the cavernous sinus: evolving ideas based on a ten year experience.

The outcomes of 114 patients with meningiomas operated at the University of Pittsburgh were analyzed. Cerebrospinal fluid leakage was the most frequent complication, observed in 25 patients (21%). Complications were more frequent in patients who had recurrent (previously operated) tumors and patients with extensive tumors. Our current analysis also indicates that patients with prior radio-therapy (usually external beam) have unacceptably high complication rates after microsurgery. Early results indicate that regrowth rates are much higher in patients with incomplete resection (20%) than those with gross total excision (5%). Of the 114 patients, 108 returned to independent living and/or their previous occupation.

Cavernous Sinus↗
PubMed1996

A scale for curriculum evaluation and development in the health professions.

Schools responsible for the education of health professionals throughout the world are seeking ways to respond to the changing realities of the health professions and society. In an effort to be responsive to as many people as possible, there is a need to develop evaluative instruments that are effective and easily understood by multiple stakeholders. The authors describe the effective utilization of a simple scale for curricular evaluation, innovation, and reform. The scale, which incorporates two previously described instruments, can be used as an aid in several phases of curricular design: (a) during the development of a statement of educational philosophies that aid in goal and objective development, (b) during the selection and organization of learning experiences, and (c) during the evaluation of a curriculum.

Curriculum↗
PubMed1980

Lack of effect of chronic renal denervation on altered sodium reabsorption during increased ureteral pressure.

The role of the renal nerves in the altered sodium reabsorption which occurs during increased ureteral pressure was studied using clearance techniques in anaesthetized rats undergoing diuresis induced by isotonic saline infusion. In rats with a sham denervated kidney, an ipsilateral increase in ureteral pressure to 20 cm H2O resulted in a marked and significant decrease in sodium and water excretion, increased fractional sodium reabsorption, and increased urine osmolality with no significant change in glomerular filtration rate. A similar significant ipsilateral increase in tubular reabsorption of sodium occurred in rats with chronically denervated kidneys during increased ureteral pressure. The changes in tubular reabsorption were rapidly reversible after return of ureteral pressure to normal. These experiments indicate that enhanced tubular reabsorption of sodium during an ipsilateral increase in ureteral pressure is not mediated by increased renal nerve activity. During the antinatriuresis of increased ureteral pressure there was a decrease in the fractional reabsorption of sodium from the opposite normal kidney. The role of the renal nerves in this compensatory change in function in the opposite kidney was studied in two further groups of animals. The renal response to a contralateral increase in ureteral pressure was similar in denervated and sham-denervated kidneys. The results indicate that altered renal nerve activity, through ipsilateral or contralateral renorenal reflexes, is not responsible for the changes in tubular reabsorption of sodium which occur during increased ureteral pressure induced by partial ureteral obstruction.

Absorption↗
PubMedDate not supplied

Silent adenoma subtype 3 of the pituitary--immunohistochemical and ultrastructural classification: a review of 29 cases.

The silent adenoma subtype 3 (SAS-3) of undetermined cellular derivation is a seemingly nonfunctioning aggressive pituitary tumor with a high recurrence rate. At the time of diagnosis SAS-3s are macro- or giant adenomas particularly aggressive in young individuals, especially women. They are usually associated with mild hyperprolactinemia and are unremarkable by histology. Immunohistochemistry, demonstrating scattered immunoreactivity mostly for GH, PRL, TSH, and alpha-subunit, is not diagnostic. Presently, only TEM permits conclusive diagnosis. Ultrastructurally, the large polar adenoma cells contain abundant RER, masses of SER, extensive multipolar Golgi apparatus, and unevenly clustered mitochondria, displaced by RER and SER, which may show close spatial relationship to RER. Cell membranes often form plexiform interdigitations. Nuclear pleomorphism and nuclear inclusions are common. The 100- to 200-nm secretory granules accumulate heavily in cell processes, which is a hallmark of glycoprotein hormone cell differentiation. The endothelial cells may contain tubuloreticular inclusions. Complete surgical removal of the large often invasive tumors is difficult necessitating postoperative treatment. SAS-3 is sensitive to conventional radiation. Some tumors express somatostatin receptors and respond well to somatostatin analogues, offering long-term control in patients with residual tumor. Possible derivation of SAS-3 from rostral thyrotrophs, a cell type presently known in rodents is contemplated.

Adenoma↗
PubMedDate not supplied

Pituitary corticotroph hyperplasia preceding adenoma in a patient with Nelson's syndrome.

We report the case of a 42-year-old woman with Cushing's disease and Nelson's syndrome. When she was 17 years old, transsphenoidal surgery was performed. A detailed morphologic study demonstrated nodular hyperplasia of corticotroph cells but no adenoma. Following a long-lasting remission (14 years), Cushing's disease recurred. After an unsuccessful second transsphenoidal surgery, Cushing's disease persisted and both adrenals were removed (at the age of 34). Subsequently the patient developed Nelson's syndrome. The pituitary tumor proved to be a corticotroph adenoma; it was removed by the transsphenoidal approach (at the age of 42). Although in most patients Cushing's disease is due to an ACTH-secreting pituitary corticotroph adenoma which precedes the manifestation of Nelson's syndrome, our case indicates not only that corticotroph hyperplasia may cause Cushing's disease but that it may exist before the development of Nelson's syndrome after the removal of both adrenals. Our study supports the view that protracted stimulation of corticotrophs resulting from the elimination of the negative inhibitory feedback effect by corticosteroids plays a role in adenoma initiation.

ACTH-Secreting Pituitary Adenoma↗