Biomedical subjects

C D Smith

Publications and source records attributed to C D Smith.

At least 127 records · Page 7Linked to original sources

PubMed1996

Laparoscopic splenectomy by the lateral approach: a safe and effective alternative to open splenectomy for hematologic diseases.

BACKGROUND: The purpose of this study was to compare the clinical outcomes and expense of laparoscopic splenectomy by the lateral approach with open splenectomy for the treatment of hematologic diseases. METHODS: Medical records of 20 matched patients undergoing open splenectomy and lateral approach laparoscopic splenectomy were retrospectively reviewed detailing perioperative course, clinical outcome, and hospital charges. RESULTS: Patients undergoing laparoscopic splenectomy (n = 10) experienced longer anesthesia (324 versus 176 minutes; p < 0.05) and operative times (261 versus 131 minutes; p < 0.05) than those undergoing open splenectomy (n = 10). No difference was noted in both intraoperative and postoperative packed red blood cells transfused. Laparoscopic splenectomy resulted in a shorter duration of nasogastric decompression (1.2 versus 2.6 days), more rapid resumption of normal oral intake (1.9 versus 4.4 days), and earlier hospital dismissal (3.0 versus 5.8 days). Although hospital charges were not significantly higher in the laparoscopic group ($17,071.00 versus $13,196.00; p > 0.05), operative charges were always significantly higher. CONCLUSIONS: When compared with open splenectomy, lateral approach laparoscopic splenectomy allows a more rapid return of normal gastrointestinal function and shorter hospital stay. The operative expense of laparoscopic splenectomy is significantly higher; however, the overall hospital expense is not. If costs can be decreased, the lateral approach laparoscopic splenectomy will be the preferred operative approach.

Adult↗

PubMed1996

Dendroamides, new cyclic hexapeptides from a blue-green alga. Multidrug-resistance reversing activity of dendroamide A.

Dendroamide A (1), one of three new bistratamide-type cyclic hexapeptides from the terrestrial blue-green alga (cyanobacterium) Stigonema dendroideum Fremy, exhibits multidrug-resistance reversing activity. The gross structures of the three compounds, dendroamides A-C, were determined by NMR and mass spectral analyses. Their absolute stereochemistries were determined by Marfey and chiral GC/MS analyses of derivatives formed from acid hydrolysis of the intact and ozonized peptides.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1996

Quantitative computed tomography and magnetic resonance imaging in aging and Alzheimer's disease. A review.

In recent aging research, quantitative techniques have been used to overcome limitations of qualitative interpretation of magnetic resonance and computed tomographic imaging. The purpose of this review is to summarize imaging results emphasizing quantitative studies using these two modalities in human aging. Magnetic resonance spectroscopy is viewed as an extension of imaging, and results of in vivo spectroscopic studies are included. Because Alzheimer's disease (AD) is closely related to aging, a discussion of quantitative imaging techniques that may distinguish normal elderly from patients with AD is included.

Aging↗

PubMed1996

Magnetic resonance imaging of the brain in Aicardi's syndrome. Report of 20 patients.

Aicardi's syndrome consists of multiple anomalies of the eye, brain, and axial skeleton in females, and is associated with early-onset infantile spasms and severe developmental delay. For the present study, magnetic resonance images of 20 patients with Aicardi's syndrome were obtained and the neuroimaging findings catalogued. These were compared to previously reported results and the findings correlated with current theories of fetal brain development. The results revealed a high frequency of cortical migration defects (94%) and a wide variability in the callosal defect, migrational abnormalities, and other findings in Aicardi's syndrome.

Abnormalities, Multiple↗

PubMed1996

Esophageal foreign bodies in children: diagnosis, treatment, and complications.

OBJECTIVE: We performed this study to identify the role of radiology in the diagnosis, treatment, and complications of esophageal foreign bodies in children. MATERIALS AND METHODS: We retrospectively reviewed the charts and radiographs of 123 esophageal foreign bodies seen in 118 children at the Medical University of South Carolina from May 1980 through May 1995. RESULTS: Most foreign bodies were coins in the upper esophagus (69%) in infants less than 2 years old (65%) for fewer than 24 hr (60%). The presenting symptoms varied, with 20% of patients asymptomatic. Respiratory symptoms that mimicked upper respiratory tract infections or croup proved misleading with long-standing foreign body retention. Preexisting esophageal disease was present in 17% of patients. The Foley catheter method of foreign body extraction was attempted in 53 cases (43%) and was successful without complications in 46 (87%). Esophagoscopy was attempted in 72 cases (58%) and was successful without complications in 66 (92%). Three patients had major complications: a fatal aorticoesophageal fistula, an extraluminal migration of a coin, and a large esophageal diverticulum. Significant mucosal erosions were shown in six patients on radiologic studies after extraction. CONCLUSION: Early recognition and treatment of esophageal foreign bodies is imperative because the complications are serious and can be life-threatening. Radiology plays an important role in the initial diagnosis, in recognition of complications, and in treatment. The Foley catheter method of foreign body extraction can be used on some patients, but esophagoscopy remains the safest method of esophageal foreign body extraction.

Adolescent↗

PubMed1996

Multi-organ erythrocyte sequestration and ligand expression in rhesus monkeys infected with Plasmodium coatneyi malaria.

The pathogenesis of human cerebral malaria is suspected to be caused by blockage of cerebral microvessels by the sequestration of parasitized human red blood cells (PRBC). Examination of infected tissues indicate PRBC sequestration in microvessels is the result of PRBC knob attachment to endothelial cell surface cytoadherence receptors such as CD36, thrombospondin (TSP), and intercellular adhesion molecule-1 (ICAM-1). In lieu of fresh human tissue, several animal models for human cerebral malaria have been developed, the Plasmodium coatneyi-infected rhesus monkey model being the most versatile. To further the understanding of noncerebral malarial complications during disease, we examined noncerebral tissues of infected rhesus monkeys. Our study demonstrated similar microvessel PRBC sequestration and the presence of cytoadherence ligands in noncerebral tissues. Immunohistochemical analysis showed CD36, TSP, and ICAM-1 cytoadherence proteins in several major organs.

Animals↗

PubMed1996

Microtubule effects of welwistatin, a cyanobacterial indolinone that circumvents multiple drug resistance.

Welwitindolinones are a family of novel alkaloids recently isolated from the blue-green alga Hapalosiphon welwitschii. We demonstrate that incubation of SK-OV-3 human ovarian carcinoma cells and A-10 vascular smooth muscle cells with welwitindolinone C isothiocyanate, now termed welwistatin, results in dose-dependent inhibition of cell proliferation, which is correlated with increases in the percentage of cells in mitosis. Treatment of A-10 cells with welwistatin resulted in reversible depletion of cellular microtubules but did not affect microfilaments. Pretreatment of A-10 cells with paclitaxel prevented microtubule depolymerization in response to welwistatin. Welwistatin inhibited the polymerization of purified tubulin in vitro but did not alter the ability of tubulin to bind [3H]colchicine or to hydrolyze GTP. Also, welwistatin did not induce the formation of topoisomerase/DNA complexes. Results of the present study indicate that welwistatin is a new antimicrotubule compound that circumvents multiple drug resistance and so may be useful in the treatment of drug-resistant tumors.

Alkaloids↗

PubMed1996

Ethical theories and principles.

Ethically sensitive situations and issues are not new in today's health care practice. They are increasing in frequency and complexity. For practitioners to face these challenges, they must not only understand their own values and beliefs, but understand the tools available to resolve these ethical dilemmas when they arise. Ethical theories and principles and decision-making models can assist the practitioner in obtaining resolution.

Attitude of Health Personnel↗

PubMed1996

Renal apoptosis and clusterin following ureteral obstruction: the role of maturation.

PURPOSE: Unilateral ureteral obstruction (UUO) increases renal apoptosis as well as clusterin, which in turn is modulated by angiotensin II. The present study was designed to investigate the role of maturation in these responses. MATERIALS AND METHODS: Neonatal and adult Sprague-Dawley rats underwent UUO or sham operation. Fourteen days later, renal apoptosis was quantitated by flow cytometry, and renal messenger RNA (mRNA) was quantitated for renin and clusterin. Apoptotic cells, macrophages, clusterin and Dolichos biflorus agglutinin were localized by immunohistochemistry. RESULTS: Following ipsilateral UUO, renal DNA content increased in the adult but decreased in the neonate. Renal macrophage infiltration induced by UUO was 2-fold greater in adults than in neonates, while distal tubular apoptosis was 2-fold greater in neonatal than in adult kidneys. Unilateral ureteral obstruction markedly increased renal renin mRNA expression in the neonate, but not in the adult, while clusterin expression was greater in adults than in neonates. Clusterin was localized to some, but not all, distal tubules containing apoptotic cells. CONCLUSIONS: We conclude that, compared with the adult, UUO in the neonate induces greater apoptosis, which in turn contributes to reduced renal DNA. This may be modulated by relative suppression of clusterin in the obstructed neonatal kidney due to greater activation of the renin-angiotensin system.

Aging↗

PubMed1996

MHC studies of the primary antiphospholipid antibody syndrome and of antiphospholipid antibodies in systemic lupus erythematosus.

OBJECTIVE: To study the association of HLA Class I, II, and III alleles with antiphospholipid antibodies, both in patients with systemic lupus erythematosus (SLE) and patients with primary antiphospholipid antibody syndrome (APS). METHODS: We studied Caucasian patients with SLE (n = 91) and with primary APS (n = 16) followed at the Ottawa General Hospital Rheumatic Disease Unit. Antiphospholipid antibodies (aPL) were defined by a positive IgG anticardiolipin antibody by serum ELISA and/or the presence of a lupus anticoagulant. HLA Class I by serology and Class II by restriction fragment length polymorphism were compared in patients with and without serum aPL, and in patients with primary APS compared to controls. C4A null alleles were studied in patients with primary APS. RESULTS: aPL were found in 19 of 91 (21%) patients with SLE, and were associated with deep venous thrombosis in this group. In patients with primary APS, stroke, deep vein thrombosis, and recurrent fetal loss were the most common clinical features. HLA-DR17(3) and Dw24 were decreased in patients with SLE with aPL and in patients with primary APS. HLA-DR4 and the linked DR53 were significantly increased in patients with primary APS compared to patients with SLE. In patients with aPL (SLE and primary APS) compared to patients with SLE without aPL, associations were found with HLA-DR53 (p = 1.5 x 10(-4), RR 5.1), DR7 (p = 0.01, RR 5.6), and to a slightly lesser degree DQ7 (p = 0.005, RR 3.6). C4A null alleles by protein allotyping and the C4A gene deletion were not associated with primary APS. CONCLUSION: We confirm the association of aPL with HLA Class II alleles. The strongest association with aPL in our study is with the HLA-DR53 haplotypes, some of which include the DQ7 allele, as suggested in an earlier study. The HLA-B8, DR17, DQ2 haplotype so closely associated with SLE is significantly decreased in both patients with aPL and with primary APS. C4A null alleles are not associated with primary APS in this population. Our study suggests the aPL response in SLE and primary APS is immunogenetically distinct from SLE itself.

Alleles↗

PubMed1995

Circumvention of P-glycoprotein-mediated multiple drug resistance by phosphorylation modulators is independent of protein kinases.

Expression of P-glycoprotein by tumor cells confers resistance to multiple natural product drugs because of its ability to export these compounds. This transporter is a substrate for several protein kinases; however, the functional significance of its phosphorylation is not defined. We examined the effects of many activators and inhibitors of protein kinases on the activity of P-glycoprotein in drug-resistant human breast carcinoma cells (MCF-7/ADR). Several phorbol esters sensitized these cells to P-glycoprotein substrate drugs; however, there was no correlation with activation of protein kinase C. The 4 alpha- and 4 beta-isomers of phorbol 12-myristate 13-acetate were equally potent in sensitizing the cells to actinomycin D and daunomycin and in increasing the intracellular accumulation of [3H]vinblastine. These effects of 4 beta-phorbol myristate acetate required much higher concentrations than were needed to increase P-glycoprotein phosphorylation and were not antagonized by staurosporine. Similar to verapamil, the phorbol esters did not sensitize MCF-7/ADR cells to cisplatin, nor parental MCF-7 cells to any of the anticancer drugs. Mezerein, K-252a, and H-89 sensitized MCF-7/ADR cells, increased intracellular accumulation of [3H]vinblastine, and antagonized photolabeling of P-glycoprotein by [3H]azidopine. Therefore, phosphorylation does not appear to play a significant role in regulating P-glycoprotein activity in MCF-7/ADR cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1995

Modulation of P-glycoprotein activity by estramustine is limited by binding to plasma proteins.

BACKGROUND: Estramustine previously has been shown to interact with P-glycoprotein and to restore intracellular accumulation of vinblastine and paclitaxel in cells overexpressing this drug transporter. However, the ability of estramustine to potentiate the cytotoxicities of several drugs was less than that expected. To resolve this apparent discordance, the authors examined the effects of serum on the actions of estramustine. METHODS: The cytotoxicities of anticancer drugs with or without estramustine or verapamil toward MCF-7 breast carcinoma cells and a P-glycoprotein-overexpressing subline MCF-7/ADR were determined using the sulforhodamine-binding assay. The extent of intracellular accumulation of [3H]vinblastine and [3H]paclitaxel was determined for each using standard methods, and the binding of radiolabeled drugs to plasma proteins was characterized by equilibrium dialysis. RESULTS: Without serum, the sensitivities of MCF-7/ADR cells to several P-glycoprotein-transported drugs were increased by estramustine and verapamil. Conversely, when the cells were treated with a 10% serum, the cytotoxicities of these drugs were increased by verapamil, but not by estramustine. Without serum, intracellular accumulation of [3H]vinblastine and [3H]paclitaxel by MCF-7/ADR cells was increased markedly by verapamil and estramustine; however, serum suppressed the effects of estramustine much more strongly than those of verapamil. Equilibrium dialysis experiments demonstrated that [3H]estramustine binds to plasma proteins, predominantly albumin, whereas [3H]paclitaxel binds to albumin and alpha 1-acid-glycoprotein, and [3H]vinblastine binds predominantly to alpha 1-acid-glycoprotein. CONCLUSION: Although estramustine can bind to P-glycoprotein, its effectiveness as a reversing agent in vivo likely is limited by binding to plasma proteins.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1995

Brain metabolism in hypothyroidism studied with 31P magnetic-resonance spectroscopy.

Metabolic consequences of hypothyroidism in adult human brain, despite neuropsychological symptoms, have not been reported. We used 31P nuclear magnetic-resonance spectroscopy of the frontal lobe to examine the effect of acute hypothyroidism on cerebral metabolism. Paired analysis showed that the phosphocreatine/inorganic-phosphate (PCr/Pi) ratio increased from a median of 2.04 (interquartile range 0.15) to 2.22 (0.25) after treatment with levothyroxine (p = 0.01). These reversible alterations in adult cerebral phosphate metabolism during acute hypothyroidism parallel PCr/Pi ratio changes described in skeletal muscle. This is the first direct evidence of cerebral metabolic effects of hypothyroidism on adult brain.

Acute Disease↗

PubMed1995

Incidence and management of pancreatic and enteric fistulas after surgical management of severe necrotizing pancreatitis.

OBJECTIVE: To determine the incidence, type, and outcome of complications of necrotizing pancreatitis. SETTING: Major tertiary referral center (Mayo Clinic, Rochester, Minn). PATIENTS: Sixty-one patients seen from 1985 to 1994 who underwent surgical management of severe necrotizing pancreatitis and who developed pancreatic or gastrointestinal fistulas. MAIN OUTCOME MEASURES: Incidence, management, and outcome of pancreatic and gastrointestinal fistulas. RESULTS: Twenty-five patients (41%) developed pancreatic (14 patients) and/or gastrointestinal tract cutaneous (19 patients) fistulas. While three duodenal fistulas and one colonic fistula were recognized at the initial operation for pancreatic necrosectomy, the remainder developed 4 to 60 days after the initial operation. Spontaneous closure occurred in nine of 14 pancreatic, two of two gastric, two of four enteric, two of eight colonic, and four of five duodenal fistulas. Mortality of the group with fistulas was 24% (6/25) and was not different from the mortality of the patients with necrotizing pancreatitis without fistulas (28% [10/36]). CONCLUSIONS: Pancreatic and gastrointestinal tract fistulas are common complications of surgical treatment of severe necrotizing pancreatitis. Well-controlled gastric, pancreatic, and enteric fistulas have the greatest likelihood of spontaneous closure. Duodenal and colonic fistulas may need surgical intervention for control or repair. Mortality in these patients parallels the mortality for severe necrotizing pancreatitis.

Colonic Diseases↗

PubMed1995

Frontal lobe phosphorus metabolism and neuropsychological function in aging and in Alzheimer's disease.

31P Magnetic resonance spectroscopy of the frontal lobe was performed in 17 patients with Alzheimer's disease (AD), 8 elderly controls (EC), and 17 young controls (YC). The phosphocreatine/inorganic phosphate (PCr/Pi) ratio in AD (2.32 +/- 0.26 SD) was significantly lower than in EC (2.65 +/- 0.41). In AD patients, a correlation was observed between the PCr/Pi ratio and the dementia rating scale (r = -0.50, p = 0.04). A significant positive correlation between PCr/Pi ratio and age was observed in both AD (r = 0.67, p = 0.003) and YC (r = 0.63, p = 0.006) groups, however, suggesting caution in interpretation of this ratio in AD. We did not find differences between AD, EC, or YC in any other spectroscopic measure. A significant sex difference in the phosphomonoester/phosphodiester ratio (PME/PDE) ratio was observed in AD brain. Females had a lower PME/PDE ratio than males.

Adult↗

PubMed1995

Prosodic characteristics of speech pre- and post-right hemisphere stroke.

Case-control studies have shown right hemisphere specialization in the production of intonation in speech. We examined spontaneous prosody in audiotapes of interviews with a 77-year-old right-handed woman recorded 6 months before and 6 weeks after she suffered a stroke affecting the right frontotemporo-parietal regions and the right basal ganglia. Post-stroke, the patient had a normal Mini-Mental Status Examination Score of 29, hemispatial neglect, and impairments in the comprehension of facial expression and prosody. Self-rated mood was within normal limits. We compared beginning, peak, and ending fundamental frequencies (fo) in breath groups, the timing of these fo changes, rate of speech, pause duration, and breath-group duration. We found that post-stroke, the patient had a more restricted fo contour, no changes in the timing of peak fo, an increased rate of speech, less variability in pause duration, and no changes in breath-group duration.

Affect↗

PubMed1995

Assessment of primary neuronal culture as a model for soman-induced neurotoxicity and effectiveness of memantine as a neuroprotective drug.

An in vitro mammalian model neuronal system to evaluate the intrinsic toxicity of soman and other neurotoxicants as well as the efficacy of potential countermeasures was investigated. The link between soman toxicity, glutamate hyperactivity and neuronal death in the central nervous system was investigated in primary dissociated cell cultures from rat hippocampus and cerebral neocortex. Exposure of cortical or hippocampal neurons to glutamate for 30 min produced neuronal death in almost 80% of the cells examined at 24 h. Hippocampal neurons exposed to soman for 15-120 min at 0.1 microM concentration caused almost complete inhibition (> or = 90%) of acetylcholinesterase but failed to show any evidence of effects on cell viability, indicating a lack of direct cytotoxicity by this agent. Acetylcholine (ACh, 0.1 mM), alone or in combination with soman, did not potentiate glutamate toxicity in hippocampal neurons. Memantine, a drug used for the therapy of Parkinson's disease, spasticity and other brain disorders, significantly protected hippocampal and cortical neurons in culture against glutamate and N-methyl-D-aspartate (NMDA) excitotoxicity. In rats a single dose of memantine (18 mg/kg) administered 1 h prior to a s.c. injection of a 0.9 LD50 dose of soman reduced the severity of convulsions and increased survival. Survival, however, was accompanied by neuronal loss in the frontal cortex, piriform cortex and hippocampus.

Acetylcholine↗

PubMed1995

Update on the analysis of the need for pediatric surgeons in the United States.

UNLABELLED: Accurate estimations of pediatric surgical manpower needs are necessary if this specialty is to avoid the consequences of under- or oversupply, and reasonable decisions must be made relative to the number of training programs needed. METHODS: Fifteen, 10, and 5 years ago, pediatric surgeons (PSs) in 62 standard metropolitan statistical areas (SMSAs) having a population of at least 200,000 were asked to estimate the number of PSs needed in their localities. A computer program analogous to the SOSSUS program was designed to project the number of PSs that would result from various numbers of trainee graduates per year. The program has been updated for comparison. Known input data included the present number and age of PSs, age range of trainees, current US population projections to the year 2025, and the average retirement age. RESULTS: These PSs estimated that 88 additional PSs are needed in the next 10 years. Currently, 26 programs in the United States graduate an average of 24 trainees per year, and six programs in Canada graduate six trainees per year. The previous projection indicated that 20 trainees per year would result in 525 PSs in 1993, and the actual number is 559; so the figures indicate that 27 or 28 PSs are entering practice each year. The apparent increase in numbers is related to entry of Canadian trainees primarily, and a few others, into practice. The current computer projection indicates that 20 graduate trainees per year would result in an absolute increase of 0.55% per year, and 25 per year would result in an increase of 1.43% per year, to 2020, while the increases in the US population would be 1.02% per year for all ages and 0.52% for 0 to 15 year olds. If all programs currently being considered for approval are certified, as many as 36 trainees per year--or 7 times the rate of the 0-15-year population increase--will result. CONCLUSION: Although an average of 20 graduates per year entering practice would keep pace with the pediatric population, 25 to 27 graduates per year--or 3.5 to 4 times the rate of the 0- to 15-year population increase--can be accommodated now into the current system of delivery of pediatric surgical care on the basis of estimated need. Many more graduates than this would create an excess of surgeons before long.

Canada↗