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Biomedical subjects

G Steele

Publications and source records attributed to G Steele.

At least 19 recordsLinked to original sources
PubMed2005

Understanding the polymorphic behavior of sibenadet hydrochloride through detailed studies integrating structural and dynamical assessment.

Three polymorphs of sibenadet hydrochloride (AR-C68397AA, Viozan) have been shown to exist at ambient temperature and have been characterized. Each undergoes a solid-state transition to a common high temperature form, which melts at approximately 220 degrees C. X-ray powder diffraction (XRPD) indicates that Polymorphs I and II share a similar layered structure not exhibited by Polymorph III. All three ambient temperature polymorphs show evidence of varying degrees of dynamic disorder of the terminal phenyl group as shown by solid-state NMR spectroscopy. Furthermore, the carbons alpha to the ether link also undergo different rates of mobility in Polymorphs I and II. This variation in the extent of dynamic disorder results in an alteration in the short-range structure resulting in distinct polymorphs. Polymorph I is the thermodynamically stable form at room temperature as indicated by solution calorimetry and assessment by thermodynamically driven solution mediated phase transition studies. The present study aims to address the types of discriminatory data required to make a clear distinction between physical forms and define, unequivocally, the presence of polymorphism.

Adrenergic beta-2 Receptor Agonists↗
PubMed2001

Characteristics of the pediatric/adolescent low-vision population at the Illinois School for the Visually Impaired.

BACKGROUND: There are few descriptive studies of children and adolescents with low vision in the United States. Our study describes a pediatric/adolescent population at the Illinois School for the Visually Impaired (ISVI), detailing the etiologies of low vision and the devices prescribed. METHODS: A retrospective record review was conducted of 260 consecutive students who had been examined at the twice-yearly Lions of Illinois Low Vision Clinic at ISVI between the years 1991 and 1999. Data collected included age, race, sex, best-corrected visual acuity, ocular diagnoses, the etiology of low vision (if known), and low-vision devices prescribed. RESULTS: The population was 60% male. Ages ranged from less than 1 year to 20 years of age. The mean best-corrected distance visual acuity was approximately 20/200. Optic atrophy, cataracts, and retinopathy of prematurity were significant etiologies of low vision; however, the largest group of patients had a diagnosis classified as "other." Hand-held telescopes, bifocals/high adds, and tinted lenses were the major low-vision devices prescribed. CONCLUSIONS: While optic atrophy, cataracts, and retinopathy of prematurity were common causes of vision impairment among students at ISVI, the largest group of students had an etiology from a wide range of disorders. Information on the causes of low vision can help with decisions on the allocation of research funds and resources for low-vision devices.

Adolescent↗
PubMed2000

Effect of resident call status on ABSITE performance. American Board of Surgery In-Training Examination.

BACKGROUND: Long work hours that result in fatigue may adversely affect cognitive function. Chronically sleep-deprived surgical residents fear that being on call the night before sitting for a standardized test puts them at a potential disadvantage. We examined American Board of Surgery In-Training Examination (ABSITE) scores to assess the effect of call status on exam performance. METHODS: Results of the 1994 ABSITE for 424 residents in 15 New England general surgery programs were collected. We compared standard scores of residents for the total test, clinical management, and basic science components with resident call status (on/off) for the night before the exam. RESULTS: Differences were apparent in total test scores (mean: off, 496.1; on, 466.0; P <.03) and clinical management scores (mean: off, 504.3; on, 470.6; P <.02) (t test, Mann-Whitney U test). Multivariate analyses revealed that differences in postgraduate year level and training track were significant contributors to differences in scores in all test components (analysis of covariance). Call status was not a significant factor in score variation after adjusting for these 2 factors. CONCLUSIONS: Differences in ABSITE scores of residents were related to postgraduate year level and training track. Call status had no significant effect on ABSITE performance.

Cognition↗
PubMed2000

Blood lead levels and vision.

Childhood exposure to lead remains a considerable public health concern. Exposure to lead can cause deficits in the visual system and visual perceptual skills. Optometrists should perform a simple personal-risk screening questionnaire when children manifest visual perceptual symptoms or difficulty in school. In addition, optometrists should be able to act as an information resource for parents with children at risk for elevated BLLs.

Animals↗
PubMed2000

Current protocols and outcomes of local therapy for rectal cancer.

Rectal cancer is a devastating disease, with patients fearing the disease and the potential treatments that may alter sexual function, genitourinary function, and overall body image. Defining the precise role for less morbid approaches to this disease, such as local excision, is of critical importance in providing optimal care in the future. This article discusses endocavitary radiation and fulguration, local excision, and prospective studies.

Brachytherapy↗
PubMed1999

Persistent hyperplastic primary vitreous with myopia: a case study.

BACKGROUND: Persistent hyperplastic primary vitreous (PHPV) is a congenital disorder that manifests a range of ocular anomalies, including leukocoria, microphthalmia, cataract, and a retrolental fibrovascular membrane. In general, the prognosis for visual acuity with PHPV has been poor. A recent report on six patients who have myopia associated with PHPV showed that these patients were not microphthalmic, did not manifest leukocoria, and showed a mean visual acuity at final followup of 20/160. CASE REPORT: The case of a 3-year-old boy with myopic PHPV of the left eye is presented. Full-time wear of the cycloplegic refraction, combined with patching of the non-amblyopic eye, resulted in an improvement in visual acuity. RESULTS: PHPV with myopia may constitute a distinct subtype of PHPV. Patients with myopic PHPV tend to seek treatment later than patients with anterior or posterior PHPV as a result of the lack of microphthalmia and leukocoria. These individuals do not show the long-term complications, such as secondary glaucoma and intraocular hemorrhages, associated with PHPV. CONCLUSION: The acuity improvement in this case of myopic PHPV suggests that a more conservative approach to its surgical management may be appropriate while pursuing refractive correction and amblyopia therapy to attain the best acuity possible.

Child, Preschool↗
PubMed1998

Geldanamycin-induced cytotoxicity in human colon-cancer cell lines: evidence against the involvement of c-Src or DT-diaphorase.

We investigated two of the major proposed modes of action of the benzoquinoid ansamycin geldanamycin using a pair of human colon-carcinoma cell lines, BE and HT29. One potential mechanism of action in colorectal cancer is the inhibition of c-Src kinase activity, since this proto-oncogene is hyperexpressed in human large-bowel tumours. Our results show that despite the 9-fold higher level of c-Src kinase activity found in HT29 cells, there was only a 1.4-fold difference in cytotoxicity as compared with BE cells, the latter being the most sensitive. Moreover, even at concentrations of geldanamycin that resulted in cell kill of 80% or more after a 24-h period of exposure, there was no effect on c-Src kinase activity in HT29 cells, although c-Src protein was depleted at supralethal levels of exposure. We also investigated the metabolism of the quinone moiety of geldanamycin by DT-diaphorase, an enzyme that activates certain quinone antibiotics such as mitomycin C and is hyperexpressed in colorectal cancer cells. Geldanamycin was shown to be a substrate for DT-diaphorase present in HT29 cells. However, the lack of a major differential in cytotoxicity between HT29 and BE cells indicates that this is unlikely to be pharmacologically significant, since the former contains high levels of enzyme activity, whereas BE cells have no significant activity due to a point mutation in the DT-diaphorase (NQO1) gene. Although reduction of geldanamycin was also catalysed by non-DT-diaphorase reductases in HT29 and BE cells, providing the potential for free radical induction, this is unlikely to be significant since studies previously reported by us elsewhere showed that cells exposed to geldanamycin exhibited no evidence of DNA damage. Thus, as far as the mode of action of geldanamycin in human colon-carcinoma cells is concerned, the present results rule out two major possibilities, namely, the involvement of c-Src tyrosine kinase inhibition and DT-diaphorase metabolism.

Antibiotics, Antineoplastic↗
PubMed1998

Overexpression of pp60c-src elicits invasive behavior in rat colon epithelial cells.

BACKGROUND & AIMS: Src activation is reported as an early event found in preneoplastic colonic adenomas and in 70% of colon carcinomas. The aim of this study was to identify the biological consequences of c-src overexpression in rat colon epithelial cells. METHODS: Introduction and overexpression of c-src in an immortalized rat colon epithelial cell line was achieved using lipofection. Transfectants were tested for changes in growth and cell behavior using different in vitro assay systems. RESULTS: Colon epithelial cells overexpressing c-src showed the ability to form microcolonies in soft agar without acquiring tumorigenic potential. In in vitro assays, c-src transfectants displayed a gain of invasive potential through Matrigel without an accompanying change in migrational ability. No discernible qualitative changes were observed in the phosphotyrosyl protein profile between c-src and v-src transfectants. Assessment of the cadherin/catenin status in these cells revealed an intact, functional complex with no detectable tyrosine phosphorylation of different components of the complex. CONCLUSIONS: Overexpression of c-src in an immortalized rat colon epithelial cell line does not elicit full neoplastic transformation but enhances anchorage-independent growth and confers invasion capability. Increased invasion through Matrigel was not linked to inactivation of the cadherin complex in c-src transfectants.

Animals↗
PubMed1998

Domestic violence training program for residents.

Domestic violence is occurring in epidemic proportions in the United States. Recent surveys have shown there is a need for educational programs for health care professionals. This report presents the results of a domestic violence workshop developed to increase knowledge and improve attitudes and skills in working with victims of domestic violence. The results of the workshop, measured by preintervention and postintervention attitude, knowledge, and skills surveys, are promising. There was a significant improvement in knowledge, self-assessed skills, and attitudes after the workshop. Although the full magnitude of the changes was not sustained over time, there was still significant improvement after 6 months in knowledge and attitude. Rates of detection and documentation did not change. Future educational programs will need to address maintaining routine screening for domestic violence in the primary care setting and to highlight more clearly the role of health care professionals in the detection and treatment of domestic violence.

Adult↗
PubMed1997

Locally advanced rectal carcinoma: pelvic control and morbidity following preoperative radiation therapy, resection, and intraoperative radiation therapy.

PURPOSE: To determine the impact of intraoperative radiation therapy (IORT) combined with preoperative external beam irradiation and surgical resection in patients with locally advanced, unresectable rectal carcinoma. METHODS AND MATERIALS: Between 1982 and 1993, 40 patients with locally advanced colorectal cancer unresectable at initial presentation were treated with preoperative external beam radiation therapy (median dose 50.4 Gy). Thirty patients received concurrent 5-fluorouracil. Twenty-seven patients had primary tumors and 13 had recurrent disease; 1 patient had a solitary hepatic metastasis at the time of surgery. Four to 6 weeks after radiation, surgical resection was undertaken, and if microscopic or gross residual disease was encountered, IORT was delivered to the tumor bed. Patients with an unevaluable or high-risk margin were also considered for IORT. IORT was delivered through a dedicated 300-kVp orthovoltage unit. The median dose of IORT was 12.5 Gy (range 8-20). The dose was typically prescribed to a depth of 1-2 cm. The median follow-up was 33 months (range 5-100). RESULTS: Thirty-three patients were able to undergo a curative resection (83%). Five patients had gross residual disease despite aggressive surgery. Seven patients did not receive IORT: six because of clear margins, and one with gross disease that could not be treated for technical reasons. The remainder of the patients (26) received IORT to the site of pelvic adherence. The crude local control rates for patients following complete resection with negative margins were 92% for patients treated with IORT and 33% for patients without IORT. IORT was ineffective for gross residual disease. Pelvic control was none of four in this setting. The crude local control rate of patients with primary cancer was 73% (16 of 22), as opposed to 27% (3 of 11) for these with recurrent cancer. The 5-year actuarial overall survival and local control rates for patients undergoing gross complete resection and IORT were 64% and 75%, respectively. Seventeen of the 26 patients (65%) who received IORT experienced pelvic complications, as opposed to two patients (28%) who did not receive IORT. The incidence of complications was similar in the patients with primary versus recurrent disease. All cases were successfully treated with the placement of a posterior thigh myocutaneous flap. Of note, no pelvic osteoradionecrosis was seen in this series. CONCLUSION: Patients with locally advanced carcinoma of the rectum were aggressively treated with combined modality therapy consisting of preoperative external beam radiotherapy, surgery, and IORT. The pelvic control rate was 82% for patients with minimal residual disease. IORT failed to control gross residual disease. The incidence of pelvic wound healing problems was 65% in this series; however, a reconstructive procedure which replaced irradiated tissue with a vascularized myocutaneous flap was successful in treating this complication. We believe that IORT has therapeutic merit in the treatment of locally advanced rectal cancer, particularly in the setting of minimal residual disease.

Adult↗
PubMed1997

Selective chemoembolization in the management of hepatic metastases in refractory colorectal carcinoma: a phase II trial.

PURPOSE: Metastatic involvement of the liver frequently determines the evolution of the clinical picture in colorectal cancer patients. We examined the efficacy and toxicity of chemoembolization in this setting, identifying prognostic factors to define patients most likely to benefit from the procedure. METHODS: Forty patients underwent chemoembolization of metastatic liver lesions from colorectal carcinoma. Selective angiography of the hepatic artery was performed to identify the feeding vessels of the metastatic lesions. The injected chemoemulsion consisted of 1,000 mg of 5-fluorouracil, 10 mg of mitomycin C, and 10 ml of ethiodized oil in a total volume of 30 ml. Gelfoam embolization then followed, until stagnation of blood flow was achieved. Patients were evaluated for response, overall survival, and toxicities. RESULTS: Overall median survival from date of first chemoembolization was ten months. Factors that predicted a longer median survival included favorable performance status (24 months), serum alkaline phosphatase and lactate dehydrogenase levels less than three times normal (24 and 12 months, respectively), and metastatic disease confined to the liver (14 months). Most patients tolerated the procedure well. The most common side effects were transient fevers, abdominal pain, and fatigue. Three patients died within one month from the procedure. CONCLUSION: This study suggests that chemoembolization of hepatic metastases in colorectal cancer should be further evaluated; it may be beneficial in patients who have failed systemic chemotherapy, have a good performance status, and have metastatic disease confined to the liver.

Abdominal Pain↗
PubMed1997

Prospective evaluation of local excision for small rectal cancers.

OBJECTIVE: Most data on local excisions for rectal cancer are based on retrospective studies. We review the results of a prospective registry of patients eligible for local excision of rectal cancer using a transanal, transsphincteric, or transcoccygeal technique combined with multimodality therapy for lesions penetrating the muscularis propria (T2) or perirectal fat (T3). METHODS: Patients with lesions less than 4 cm in diameter and less than 10 cm from the dentate line, with no evidence of distant metastases or invasion into the perirectal fat, were eligible for local excision. Patients with invasion into the muscularis propria (T2) or greater (T3) received adjuvant chemoradiation therapy. RESULTS: Forty-eight patients have been followed prospectively. Average age is 63 years. Thirty-three patients underwent a transanal excision. Fifteen patients underwent either a transsphincteric or technique excision. There was no perioperative mortality. Pathology revealed 1 Tis, 21 T1, 21 T2, and 5 T3 cancers. Mean follow-up is 40.5 months. Cancer-related overall mortality was 4 percent. Overall local or distant recurrence rate was 8 percent (4/48). Recurrence appeared to be related to presence of a positive margin or aggressive histology (lymphatic invasion). Local recurrences were treated with salvage therapy. CONCLUSION: Local excision can be used selectively for small rectal cancers, with minimum morbidity. Recurrence rates are low (8 percent). Patients with either a positive margin or lymphatic invasion need to be considered for further therapy, including abdominoperineal resection, even with T1 lesions. Adjuvant chemoradiation appears to be a benefit for all T2 or T3 cancers.

Adenocarcinoma↗
PubMed1997

Spiral computerized tomography in the evaluation of acute flank pain: a replacement for excretory urography.

PURPOSE: We determined the value of noncontrast enhanced spiral computerized tomography (CT) in the evaluation of suspected renal colic. MATERIALS AND METHODS: Thin section (5 mm.) noncontrast enhanced CT was used to evaluate 100 patients presenting to the emergency room with flank pain. The 55 patients with ureteral obstruction were followed at the urology outpatient clinic and by telephone interview, while 45 without ureteral obstruction were followed by telephone interview and chart review. Sensitivity, specificity, and positive and negative predictive values for CT were determined, with passage, retrieval or identification of a stone on a retrograde study considered the gold standard for diagnosis. RESULTS: A total of 89 patients had adequate clinical followup to assess outcome accurately. Of 55 patients with ureteral obstruction on CT 11 underwent endoscopic stone removal, while 44 were treated conservatively with stone passage documented in 39. Of the 45 patients without ureteral stones identified 38 did not pass calculi and CT provided a definite diagnosis in 14. There was 1 false-negative study. The results yielded 98% sensitivity, 100% specificity, and 100% positive and 97% negative predictive values. CONCLUSIONS: Noncontrast enhanced spiral CT was accurate and reliable in detecting obstructing ureteral calculi in patients with flank pain.

Acute Disease↗