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Biomedical subjects

H S Bell

Publications and source records attributed to H S Bell.

At least 19 recordsLinked to original sources

A telephone needs assessment for potential high utilizers.

BACKGROUND AND OBJECTIVES: We conducted a telephone needs assessment of patients at risk for high utilization of health services to determine the type of intervention that might be most responsive to their needs. METHODS: Family practice patients who were classified as at high risk based on self-reported health-related quality of life (HRQOL), age, and gender received a structured telephone interview to ask about their health problems, difficulties with their health care, and types of help programs that might be useful to them. RESULTS: Of 867 adult patients randomly selected as eligible for the study, 352 completed the Duke Health Profile to measure HRQOL, 122 were classified at risk for high utilization, and 104 were interviewed by telephone. Patient-reported health problems were similar to provider-reported problems. High-risk patients reported difficulties receiving help from the clinic on issues of communication and logistics (43.9%), limitations of clinic facilities and services (26.3%), and financial concerns (26.3%). Of the highest risk patients, 45.8% expressed willingness to participate in help programs conducted over the telephone. CONCLUSIONS: Many high-risk patients might benefit from participation in a telephone intervention program. A future study is needed to measure the effectiveness of such a program to improve utilization of health services.

Adult↗

Expression of poly(ADP-ribose) polymerase and distribution of poly(ADP-ribosyl)ation in glioblastoma and in a glioma multicellular tumour spheroid model.

Development of necrosis is a characteristic feature of glioblastoma but its pathogenesis remains poorly understood. The process of poly(ADP-ribosyl)ation in response to DNA damage is mediated by poly(ADP-ribose) polymerase (PARP) and results in NAD+ depletion. The consequent ATP and energy depletion may result in cell necrosis. Therefore PARP activation is a potential candidate for a regulatory role in the pathogenesis of necrosis in glioblastoma. This study investigated whether there might be a relationship between both PARP expression and poly(ADP-ribosyl)ation, and necrosis in glioblastoma. The pattern of expression of PARP and of poly(ADP-ribose) groups in an archival series of glioblastoma was examined using immunohistochemistry. These parameters were also studied in multicellular tumour spheroids, derived from human glioma cell lines in which central necrosis develops with increasing spheroid diameter. Poly(ADP-ribose) groups were expressed in peri-necrotic tumour cells in glioblastoma. In the spheroid model poly(ADP-ribosyl)ation was seen centrally in pre-necrotic and necrotic cells with increasing spheroid diameter. PARP was widely expressed in viable tumour cells in the glioblastoma sections. In the spheroids, PARP expression, which was initially diffuse, became confined to the outer proliferative zone with increasing diameter. The pattern of expression of poly(ADP-ribose) groups in the spheroids and in glioblastoma raises the possibility that poly(ADP-ribosyl)ation may play a role in the development of necrosis in glioma. The high basal PARP expression in both glioblastoma and the spheroids suggests that this enzyme may have additional roles in glioma cell biology.

Adult↗

The effects of chronic nitric oxide synthase suppression on glioma pathophysiology.

Nitric oxide synthase (NOS) is strongly expressed in glioma and has an important role in tumour blood flow (TBF) regulation. Whether manipulation of NOS function within a tumour can have any therapeutic effect is unknown. This study therefore evaluated the pathophysiological effects of chronic systemic NOS inhibition on experimental rodent glioma blood flow, growth and necrosis. To determine the duration and pathophysiological effects of systemic NOS inhibition, Ng-nitro-L-arginine methyl ester (L-NAME) was given to rats bearing C6 glioma acutely (single dose i.v., 30 mg kg) or for either 4 or 7 days (i.p. 75 mg kg day) prior to study. TBF and local cerebral blood flow (LCBF) were measured using C14-iodoantipyrine quantitative autoradiography. Tumour volume, tumoural necrosis and tumoural NOS were measured using conventional neuropathology and immunocytochemistry. Acute and 4-day L-NAME administration produced significant TBF reductions (-48 and -39%, respectively) with less marked changes in LCBF (-35 and -15%, respectively). Seven-day L-NAME administration reduced tumour volume (p = 0.12), increased tumoural necrosis (p < 0.05), but immunohistochemistry showed no difference in tumoural NOS expression. These results confirm that NOS has a significant role in the pathophysiology of experimental glioma, and that in this glioma model the effects of chronic systemic NOS inhibition are, for the period under study, predominately anti-tumoural. Whether chronic NOS inhibition is useful as an adjunct in glioma therapy or provides the opportunity for novel therapeutic approaches requires further study.

Animals↗

Controlling blood glucose levels in patients with type 2 diabetes mellitus. An evidence-based policy statement by the American Academy of Family Physicians and American Diabetes Association.

OBJECTIVE: To review evidence about the benefit of intensive glycemic control for patients with type 2 diabetes and to develop practice recommendations. PARTICIPANTS: A 9-member panel composed of family physicians, general internists, endocrinologists, and a practice guidelines methodologist was assembled by the American Academy of Family Physicians, the American Diabetes Association, and the American College of Physicians. EVIDENCE: Admissible evidence included published randomized controlled trials and observational studies regarding the effects of glycemic control on microvascular and macrovascular complications and on adverse effects. We followed systematic search and data abstraction procedures. Greater weight was given to clinical trials and to evidence about health outcomes. CONSENSUS PROCESS: Interpretations of evidence and approval of documents were finalized by unanimous vote, with recommendations linked to evidence and not expert opinion. The full report was prepared by the chair and 2 panel members, representing each of the 3 organizations. The initial draft underwent external review by 14 diabetologists and family physicians and changes consistent with the evidence were incorporated. CONCLUSIONS: The evidence demonstrates that the risk of microvascular and neuropathic complications is reduced by lowering glucose concentrations. Whether glycemic control affects macrovascular outcomes is less clear. The potential benefits of glycemic control must be balanced against factors that either preempt benefits (eg, limited life expectancy, comorbid disease) or increase risk (eg, severe hypoglycemia). The magnitude of benefit is a function of individual clinical variables (eg, baseline glycated hemoglobin level, presence of preexisting microvascular disease). Appropriate targets for treatment should be determined by considering these factors, patients' risk profiles, and personal preferences.

Aged↗

Effects of N-6 essential fatty acids on glioma invasion and growth: experimental studies with glioma spheroids in collagen gels.

OBJECT: Intracranial infusions of gamma-linolenic acid (GLA), an essential fatty acid, have been used as an adjuvant therapy following malignant glioma resection; however, little is known about the dose response of glioma cells to this therapy. In this in vitro study the authors address this important pharmacological question. METHODS: Glioma spheroids derived from U87, U373, MOG-G-CCM, and C6 cell lines were grown in collagen gel and exposed to a range of GLA concentrations (0-1 mM) for 5 days. The diameter of glioma spheroids was measured, the apoptotic index was assessed using both the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling technique and cell morphological testing, and the levels of proliferating cell nuclear antigen were also measured. CONCLUSIONS: The dose-response patterns were similar for all four glioma spheroids. Low concentrations of GLA (<100 microM) increased both apoptosis and proliferation with a net increase in tumor growth and invasion, whereas high-dose GLA (>100 microM) significantly impaired spheroid cell growth. The proliferative effects of low-dose GLA could be a hazard in the clinical treatment of malignant glioma; however, because of the low toxicity of GLA against normal cells, local delivery of millimolar doses of GLA could significantly reduce tumor size.

Animals↗

Minor head injury in children: current management practices of pediatricians, emergency physicians, and family physicians.

OBJECTIVE: To describe variation in the clinical management of minor head trauma in children among primary care and emergency physicians. DESIGN: A survey of pediatricians, family physicians, and emergency physicians drawn from a random sample of members of the American Academy of Pediatrics, the American Academy of Family Physicians, and the appropriate American Medical Association specialty listings, respectively. Physicians were given clinical vignettes describing children presenting with normal physical examination results after minor head trauma. Different clinical scenarios (brief loss of consciousness or seizures) were also presented. Information was gathered on initial and subsequent management steps most commonly used by the physician. RESULTS: Surveys were returned by 765 (51%) of 1500 physicians. Of these, 303 (40%) were pediatricians, 269 (35%) family practitioners, and 193 (25%) emergency physicians. For minor head trauma without complications, observation at home was the most common initial physician management choice (n = 547, 72%). Observation in office or hospital was chosen by 81 physicians (11%). Head computed tomographic (CT) scan was chosen by 7 physicians (1%) and skull x-ray by 24 physicians (3%) as the first management option. Most physicians (n = 445, 80%) who initially chose observation at home would obtain a CT scan if the patient showed clinical deterioration. In the original scenario, if the patient had also sustained a loss of consciousness, 383 physicians (58%) altered management. Of these, 120 (18%) chose CT, 13 (2%) chose skull x-ray, 1 (1%) chose magnetic resonance imaging, 141 (21%) chose inpatient observation, and 125 (19%) chose a combination of CT scanning and observation. With seizures, 595 (90%) altered management, with 176 physicians (27%) choosing CT scan, 5 (1%) skull x-ray, 60 (9%) inpatient observation, and 299 (45%) a combination of radiological evaluation and observation. CONCLUSIONS: Most physicians surveyed chose clinic or home observation for initial management of minor pediatric head trauma. Clinical management was more varied when patients had sustained either loss of consciousness or seizures. Further study of the appropriate management of minor head trauma in children is needed to guide physicians in their care.

Adolescent↗

Glioma cells transduced with selection transgenes may not form gliomas in vivo and can also inhibit glioma formation by admixed wild glioma cell lines.

Following in vitro lipofection transfection of the rat glioma cell line A15A5 with the plasmid transgene CMV/HyTK, which confirms hygromycin resistance and ganciclovir sensitivity, a series of experiments was planned in which the "bystander" phenomenon would be evaluated using the rodent implantation glioma model. However examination of the brain of rodents in which the A15A5HyTK cells were implanted showed no evidence of glioma growth. Furthermore, rodents having intracerebral implantation of (i) wild A15A5 and A15A5HyTK cells in a 50/50 mix, (ii) wild A15A5 and A15A5HyTK cells in a 90/10 mixture and (iii) wild C6 and A15A5HyTK cells in a 50/50 mix all failed to grow macroscopic tumours by 15-17 days irrespective of whether the animals had been administered ganciclovir (GCV) in the week before sacrifice. Neuropathological and immunocytochemical analysis of the implantation sites showed no difference between the GCV and saline treated groups of animals for any implantation cell mix. These observations confirm previous results that suggest transduction of malignant rodent glioma cell lines with a variety of selection, oncogenic and marker genes significantly impairs their in vivo tumorigenic potential compared to the wild type cell lines. This study also demonstrates that even without GCV treatment the transduced cells inhibit, by an unknown mechanism(s), the tumorigenicity of other non transfected malignant cells. The implications of this study for gene therapy of human malignant glioma are discussed.

Animals↗

Terminal ventriculostomy for syringomyelia.

The clinical course of 12 patients who underwent terminal ventriculostomy for syringomyelia is presented. Opening the central canal at the tip of the conus medullaris is a relatively benign procedure that improves the symptoms of syringomyelia and syringobulbia. This canal normally terminates at the tip of the conus, but in each of the 12 surgical specimens it continued into the filum terminale for distances up to 8 cm. In most cases the tip of the conus was located more caudally than normal, indicating some degree of tethering in fetal life. This belief is supported by the fact that the newborn, whose conus is tethered to a lipoma at the sacral level, may develop syringomyelia in adult life.

Adult↗

Trial of labor or repeated cesarean section. The woman's choice.

OBJECTIVE: To develop recommendations for the preferred delivery method for a pregnant woman who underwent a previous low transverse cesarean section and who has no contraindications to labor. DATA SOURCES: MEDLINE searches and the references from retrieved articles yielded 759 citations. Search terms included trial of labor (TOL), trial of scar, vaginal birth after cesarean section (VBAC), and uterine rupture. STUDY SELECTION: Articles with primary outcomes data contrasting TOL and elective repeat cesarean section (ERCS) were analyzed. Studies from developing countries or before 1980 were excluded. DATA EXTRACTION: Data from 292 articles were extracted independently by at least 2 team members using a structured form. DATA SYNTHESIS: Outcome data were combined using commercially available software and are presented as absolute differences per 10,000, with 95% Bayesian confidence intervals. Maternal outcomes showed that TOL increased the risk for uterine rupture (23.9 [0.24%]); ERCS increased the risk for infection (522 [5.22%]) and bleeding (58.6 [0.59%]). Infant outcomes differed only for 5-minute Apgar scores of less than 7, which were more likely for infants whose mothers underwent TOL (85 [0.85%]). Other outcomes (eg, disability), patient preferences, and cost data did not lend themselves to meta-analysis and were examined separately. While two thirds of women desired TOL, one third preferred ERCS. Costs were 1.7 to 2.4 times greater for ERCS. CONCLUSIONS: A woman should be given information on both delivery methods and encouraged to undergo TOL, but her preference for ERCS should be respected.

Decision Making↗