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C D Smith

Publications and source records attributed to C D Smith.

At least 91 records · Page 5Linked to original sources
PubMed1999

Functional magnetic resonance imaging evidence for task-specific activation of developmentally abnormal visual association cortex.

Functional magnetic resonance imaging was performed on a 36-year-old woman with muscular dystrophy, intractable epilepsy, and bilateral temporo-occipital lissencephaly. We observed islands of task-specific activation in lissencephalic cortex homologous to visual association regions activated in normal subjects on the same visual confrontation naming task. This result suggests lissencephalic cortex may develop specific functional connections with other brain regions.

Adult↗
PubMed1999

Laparoscopic adrenalectomy: new gold standard.

Nearly 600 cases of laparoscopic adrenalectomy have been described in the world literature, documenting the safety and effectiveness of the procedure. Comparative studies have demonstrated the advantages of the laparoscopic approach when compared to traditional open approaches to adrenalectomy, documenting a more rapid and comfortable recovery, shorter hospitalization, and fewer complications. Several techniques of laparoscopic adrenalectomy have been described. We prefer the transabdominal approach in the lateral decubitus position. Herein we report our experience with 28 adrenalectomies using this approach. Indications for adrenalectomy have been hyperaldosteronism (9), hypercortisolism (4), pheochromocytoma (3), incidentaloma (6), metastasis (3), lymphoma (1), angiomyolipoma (1), other (1). Average tumor size was 3.3 cm (1. 4-8.3 cm). Average operative time was 152 minutes (110-210 minutes), with left adrenalectomy taking slightly longer to perform than on the right (156 vs. 145 minutes). There were no intraoperative complications and one conversion to open adrenalectomy for a large metastatic lung cancer found to be invading the liver. One patient experienced left rib pain from a cannula site immediately at the costal margin. There were no other complications. Average length of hospitalization was 2.3 days (1-6 days). With this and others' experience, laparoscopic adrenalectomy has become the gold standard for adrenalectomy. This manuscript reviews the literature on laparoscopic adrenalectomy and describes the transabdominal lateral approach.

Adrenal Gland Diseases↗
PubMed1999

Laparoscopic insufflation with room air causes exaggerated interleukin-6 response.

BACKGROUND: The gut is a central organ in the postoperative stress reaction. We previously reported that measuring gut-mucosal cytokines may more accurately reflect the response to operative stress. Additionally, we have shown that the gut demonstrates a blunted cytokine response after laparoscopy as compared with laparotomy. METHODS: To further investigate whether this differential response is caused by exposure of the peritoneal cavity to general atmospheric air during laparotomy, 80 A/J mice were randomized equally into four groups: CD (carbon dioxide [CO2] pneumoperitoneum), RA (room air pneumoperitoneum), AP (anesthesia and port insertion only), and PC (pure control, no intervention). Pneumoperitoneum was established and maintained at 3 mmHg for 60 min. All the mice were killed 4 h after the intervention. Jejunal mucosa and serum samples were collected and analyzed for interleukin-6 (IL-6) levels. Results were analyzed by analysis of variance (ANOVA). RESULTS: Gut-mucosal IL-6 in the RA group was significantly higher than in all other groups: RA, 1,354.5 +/- 117.9* vs. CD, 964.3 +/- 114.0 vs. AP, 960.2 +/- 86.2 vs. PC, 908.0 +/- 83.6; *p < 0.05. The CD group did not show a significant increase in gut-mucosal IL-6 as compared with the AP and PC groups. Similarly, RA resulted in significant increases in serum IL-6 as compared with AP and PC, whereas CD showed no significant difference: RA, 161.3 +/- 66.2* vs. 95.1 +/- 1 vs. AP, 10.6 +/- 5.3 vs. PC, undetectable; *p < 0.05. There was no difference in serum IL-6 level between CD or any of the other groups. CONCLUSIONS: Exposure of the peritoneal cavity to atmospheric air, independently of the trauma of abdominal access, causes an exaggerated serum and gut mucosal IL-6 response 4 h after intervention. The beneficial effect of CO2 laparoscopy may be caused by the exclusion of general atmospheric air from the peritoneal cavity.

Air↗
PubMed1999

Fundoplications resist reflux independent of in vivo anatomic relationships.

BACKGROUND: Antireflux operations restore lower esophageal sphincter (LES) function and hiatal anatomy; however, the relative contributions are unclear. METHODS: We measured the competency of fundoplications, exclusive of in vivo variables, in gastroesophageal explants from 8 cadavers. Using a multichannel manometer, esophageal, LES, and intragastric pressures were recorded during transpyloric distension. Data were compared at baseline, and after Nissen (360 degrees) and Toupet (270 degrees) fundoplications. RESULTS: Before fundoplication, stomachs refluxed immediately upon distension. Nissen fundoplications never refluxed before gastric rupture (46.8 +/- 15.0 mm Hg). LES pressure averaged 2.0 +/- 0.5 times intragastric pressure during distension. Toupet fundoplications refluxed at intragastric pressure <2 mm Hg, then became competent until gastric rupture (49.9 +/- 15.0 mm Hg). LES pressure averaged 2.4 +/- 1.0 times intragastric pressure during distension. CONCLUSIONS: Nissen and Toupet fundoplications increase LES pressure linearly at 2 to 2.5 times intragastric pressure, independent of in vivo variables. Toupet fundoplication lacks the competency of Nissen fundoplication at low intragastric pressures.

Aged↗
PubMed1999

Fundoplication provides effective and durable symptom relief in patients with Barrett's esophagus.

BACKGROUND: Columnar-lined esophagus with intestinal metaplasia (IM), also called Barrett's esophagus, is a manifestation of severe gastroesophageal reflux (GER) and may predict poor symptom relief and high failure rate after fundoplication. We compared symptom scores and reoperation rates in GER patients with and without Barrett's esophagus. METHODS: Between July 1992 and July 1997, 646 patients underwent fundoplication (626 laparoscopic). Of 150 endoscopic biopsies of suspected columnar-lined esophagus, 80 confirmed IM, 50 identified cardiac or fundic epithelium, and 20 revealed only esophagitis. Typical GER symptoms were scored by patients preoperatively and postoperatively (0 to 4 scale). We compared symptom response (Wilcoxon rank sum test) and failure rates (t test) in patients with IM and GER controls without IM. Preoperative data were available for 74 IM patients and 496 controls. One-year follow-up was available in 45 IM patients and 301 controls. Intermediate follow-up (2 to 5 years) was available in 20 IM patients and 99 controls. RESULTS: Preoperatively and postoperatively, patients with IM reported heartburn, regurgitation, and dysphagia scores similar to controls. Procedure failure, requiring redo fundoplication, appeared more likely in IM patients than controls (6.3% versus 2.5%), but this difference did not reach statistical significance (P = 0.061). CONCLUSION: Fundoplication provides equivalent symptom relief for patients with and without IM.

Barrett Esophagus↗
PubMed1999

Laparoscopic fundoplication failures: patterns of failure and response to fundoplication revision.

OBJECTIVE: To determine rates and mechanisms of failure in 857 consecutive patients undergoing laparoscopic fundoplication for gastroesophageal reflux disease or paraesophageal hernia (1991-1998), and compare this population with 100 consecutive patients undergoing fundoplication revision (laparoscopic and open) at the authors' institution during the same period. SUMMARY BACKGROUND DATA: Gastroesophageal fundoplication performed through a laparotomy or thoracotomy has a failure rate of 9% to 30% and requires revision in most of the patients who have recurrent or new foregut symptoms. The frequency and patterns of failure of laparoscopic fundoplication have not been well studied. METHODS: All patients undergoing fundoplication revision were included in this study. Symptom severity was scored before and after surgery by patients on a 4-point scale. Evaluation of patients included esophagogastroscopy, barium swallow, esophageal motility, 24-hour ambulatory pH, and gastric emptying studies. Statistical analysis was performed with multiple chi-square analyses, Fisher exact test, and analysis of variance. RESULTS: Laparoscopic fundoplication was performed in 758 patients for gastroesophageal reflux disease and in 99 for paraesophageal hernia. Median follow-up was 2.5 years. Thirty-one patients (3.5%) have undergone revision for fundoplication failure. The mechanism of failure was transdiaphragmatic herniation of the fundoplication in 26 patients (84%). In 40 patients referred from other institutions, after laparoscopic fundoplication, only 10 (25%) had transdiaphragmatic migration (p < 0.01); a slipped or misplaced fundoplication occurred in 13 patients (32%), and a twisted fundoplication in 12 patients (30%). The failure mechanisms of open fundoplication (29 patients) followed patterns previously described. Fundoplication revision procedures were initiated laparoscopically in 65 patients, with six conversions (8%). The morbidity rate was 4% in laparoscopic procedures and 9% in open ones. There was one death, from aspiration and adult respiratory distress syndrome after open fundoplication. A year or more after revision operation, heartburn, chest pain, and dysphagia were rare or absent in 88%, 78%, and 91%, respectively, after laparoscopic revision, and were rare or absent in 91%, 83%, and 70%, respectively, after open revision, but 11 patients ultimately required additional operations for continued or recurrent symptoms, 3 after open revision (17%), and 8 after laparoscopic fundoplication (11%). CONCLUSIONS: Laparoscopic fundoplication failure is infrequent in experienced hands; the rate may be further reduced by extensive esophageal mobilization, secure diaphragmatic closure, esophageal lengthening (applied selectively), and avoidance of events leading to increased intraabdominal pressure. When revision is required, laparoscopic access may be used successfully by the laparoscopically experienced esophageal surgeon.

Fundoplication↗
PubMed1999

Neuroprotective effects of HU-211 on brain damage resulting from soman-induced seizures.

Neuroprotective effects of HU-211 (dexanabinol), a synthetic nonpsychotropic analog of tetrahydrocannabinol, on brain damage resulting from soman-induced seizures were examined in male Sprague-Dawley rats challenged with 1.6 LD50 soman. At 5 or 40 min after onset of seizures, the rats were given an intraperitoneal injection of 25 mg/kg HU-211. All rats that received soman showed electrocorticographic (ECoG) evidence of sustained seizures and status epilepticus for 4-6 hr. HU-211 had no effect on either the strength or duration of seizure activity. Administration of HU-211 at 5 min after seizure onset reduced median lesion volume 86% (as assessed by microtubule-associated protein 2 (MAP2)-negative staining), and when administered 40 min post-onset, the reduction in necrosis was 81.5% despite the presence of continuous seizures for 4-5 hr. These observations were corroborated by hemotoxylin and eosin (H&E) histopathological assessment that showed a significant reduction in piriform cortical neuronal damage in HU-211-treated animals. It is concluded that HU-211 provides considerable neuroprotection against brain damage produced by soman-induced seizures.

Animals↗
PubMed1999

MRI temporal lobe volume measures and neuropsychologic function in Alzheimer's disease.

The authors performed quantitation of the temporal lobes using magnetic resonance imaging in 20 patients with mild-to-moderate Alzheimer's disease, 20 age-matched aged control subjects, and 26 healthy young volunteers. Compared to young subjects, aged controls showed volume reductions in amygdala (17%, p = 0.02), hippocampus (15%, p = 0.0001) and temporal lobe (22%, p = 0.0001). Compared to aged controls, Alzheimer's subjects showed further volume reductions in amygdala (33%, p = 0.0001) and hippocampus (20%, p = 0.006) but not temporal lobe (7%, p = 0.15). In Alzheimer's subjects, left temporal lobe volume correlated strongly with the Mini Mental State (MMSE) score (adjusted r2 = 0.46, p = 0.0006) whereas right amygdala volume correlated inversely with the noncognitive ADAS score (adjusted r2 = 0.46, p = 0.0006). The authors conclude that significant volume changes occur in the temporal lobe in aging and in Alzheimer's disease, with the greatest percentage reductions in the amygdala in Alzheimer's disease. Temporal neocortical atrophy and temporal limbic atrophy might be associated with different patterns of performance and behavior in Alzheimer's patients.

Adult↗
PubMed1999

D-dimers in the diagnosis of pulmonary embolism.

The aim of this study was to determine if the absence of circulating D-dimers, as determined by latex agglutination assays, can correctly exclude the presence of pulmonary embolism using pulmonary angiography as the diagnostic endpoint. Blood samples were obtained prospectively at the time of angiography for suspicion of acute pulmonary embolism. Plasma was assayed for D-dimer by five different latex agglutination assays. Angiographic evidence of pulmonary emboli was found in 34% (35/ 103) of patients. The latex agglutination assays had sensitivities of 97 to 100% and specificities of 19 to 29%. The negative predictive value was 94 to 100%. However, a negative D-dimer was rare in patients with recent surgery, malignancy, or total bilirubin > 34 micromol/L (> 2 mg/dl). In 31 patients suspected of pulmonary emboli but without these confounding factors, the five D-dimer assays were negative in 46 to 55% of patients with normal pulmonary angiograms. The negative predictive value in these patients was 100% by all five latex agglutination assays tested. The latex agglutination assays for D-dimer, when the pulmonary angiogram is used as the diagnostic endpoint and in the absence of recent surgery, malignancy, or liver disease, appears to be a clinically useful test in the diagnosis of acute pulmonary embolism.

Aged↗
PubMed1999

Frequency of first metastatic events in breast cancer: implications for sequencing of systemic and local-regional treatment.

PURPOSE: The sequencing of treatment for early breast cancer is controversial. The purpose of this study was to quantify the risk of delaying surgery, using estimates of the frequency of first metastases from breast primary tumors. PATIENTS AND METHODS: The probability that 560 (node-negative), 657 (with one to three positive nodes), and 505 (with more than three positive nodes) women treated without adjuvant chemotherapy would be free of distant disease at presentation was fit to a mathematical model of the seeding of distant metastases and combined with estimates of the growth rate to calculate the frequency of first distant disseminations per month. RESULTS: Frequencies of first distant metastases were approximately 1% to 2% per month, 2% to 4% per month, and 3% to 6% per month in T1 patients who were node-negative, had one to three positive nodes, or more than three positive nodes, respectively. As a result, the typical patient with T1 disease, who has a 70% to 80% chance of being free of distant disease, runs a 1% to 4% risk of distant dissemination for each month surgery is delayed. Assuming a 30% reduction in mortality caused by adjuvant chemotherapy, the model predicts that T1 patients treated with neoadjuvant chemotherapy would potentially have a higher rate of distant metastasis development than those treated with an initial surgical resection followed by adjuvant chemotherapy. CONCLUSION: We formulate the hypothesis that optimal sequencing of surgery and systemic treatment of breast cancer may be size-dependent, with a disadvantage or no benefit from neoadjuvant treatment for T1 patients but an increasing benefit with increasing size of the primary tumor.

Age Factors↗
PubMed1998

Tolyporphin: a natural product from cyanobacteria with potent photosensitizing activity against tumor cells in vitro and in vivo.

Tolyporphin (TP), a porphyrin extracted from cyanobacteria, was found to be a very potent photosensitizer of EMT-6 tumor cells grown both in vitro as suspensions or monolayers and in vivo in tumors implanted on the backs of C.B17/Icr severe combined immunodeficient mice. Thus, during photodynamic treatment (PDT) of EMT-6 tumor cells in vitro, the photokilling effectiveness of TP measured as the product of the reciprocal of D50 (the light dose necessary to kill 50% of cells) and the concentration of TP is approximately 5000 times higher than that of Photofrin II (PII), the only PDT photosensitizer thus far approved for clinical trials. TP almost exclusively localizes in the perinuclear region and specifically in the endoplasmic reticulum (ER), as shown by microspectrofluorometry on single living EMT-6 cells costained with the ER and/or Golgi fluorescent vital probes, 3,3'-dihexyloxacarbocyanine iodide and N-[4,4-difluoro-(5,7-dimethyl-BODIPY)-1-pentanoyl]-D-erythro-sphin gosine (Molecular Probes, Eugene, OR). As a result, the singlet oxygen-mediated photodynamic activity of TP induces an effective inactivation of the acyl CoA:cholesterol-O-acyltransferase, a sensitive marker of ER membrane integrity and alterations of the nuclear membrane. In vivo, with the EMT-6 mouse tumor model, an exceptional effectiveness is also observed as compared to that of PII and other second generation photosensitizers of the pheophorbide class, which are themselves much more potent than PII. The outstanding PDT activity of TP observed in vivo may be due to its unique biodistribution properties, in particular much less extraction by the liver, resulting in a higher delivery to other tissues, including tumor.

Animals↗
PubMed1998

Design, synthesis, and evaluation of the multidrug resistance-reversing activity of D-glucose mimetics of hapalosin.

When five substituents of hapalosin were placed on D-glucose, molecular modeling revealed that the substituents on mimetics 2 and 3 occupy similar spatial positions as the corresponding substituents on hapalosin. Mimetic 3 and all the glucopyranoside intermediates generated in its synthesis were assessed for their ability to reverse multidrug resistance (MDR) mediated by P-glycoprotein (P-gp) or the multidrug resistance-associated protein (MRP). None of the sugar compounds were as effective as hapalosin in inhibiting P-gp in cytotoxicity and drug accumulation assays using MCF-7/ADR cells. By contrast, four D-glucose compounds exhibited similar efficacy as hapalosin in antagonizing MRP in cytotoxicity assays with HL-60/ADR cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Pharmacokinetics, pharmacodynamics, and safety of metrifonate in patients with Alzheimer's disease.

Metrifonate is converted nonenzymatically to 2.2, dimethyl dichlorovinyl phosphate (DDVP), an inhibitor of acetylcholinesterase (AChE). This 21-day, randomized, double-blind, placebo-controlled trial of metrifonate in patients with Alzheimer's disease (n = 27) evaluated four doses, each administered orally once daily. All patients received a loading dose (LD) for 6 days followed by a maintenance dose (MD) for 15 days. The treatment groups were: panel 1, LD = 1.5 mg/kg (75-135 mg), MD = 0.25 mg/kg (12.5-25 mg); panel 2, LD = 2.5 mg/kg (125-225 mg), MD = 0.40 mg/kg (20-35 mg); panel 3, LD = 4.0 mg/kg (200-335 mg), MD = 0.65 mg/kg (30-60 mg); and panel 4, LD = 4.0 mg/kg (200-335 mg), MD = 1.0 mg/kg (50-90 mg). All metrifonate doses were well tolerated. Most adverse events were mild to moderate in intensity, gastrointestinal in nature, and transient. Mean area under the concentration-time curve (AUC) and maximum concentration (Cmax) for both metrifonate and DDVP increased in relation to dose. Metrifonate and DDVP had similar, largely dose-independent mean values for time to Cmax (tmax) and half-life (t1/2). There was little or no accumulation of either metrifonate or DDVP with long-term administration. After 21 days of treatment, mean percent erythrocyte AChE inhibition was 14%, 35%, 66%, 77%, and 82% for placebo and panels 1 through 4, respectively. Cognitive improvement was observed with the two highest metrifonate doses. These results reflect favorable safety and pharmacokinetic profiles for the use of metrifonate in the treatment of Alzheimer's disease.

Acetylcholinesterase↗
PubMed1998

GM1 monosialoganglioside pretreatment protects against soman-induced seizure-related brain damage.

The effects of GM1 monosialoganglioside pretreatment on brain damage resulting from soman-induced seizure activity were examined in this study. Male Sprague-Dawley rats were infused with GM1 via an osmotic minipump connected through a permanent cannula implanted intracerebroventricularly and challenged with soman (83 micrograms/kg, i.e., 1.25 x LD50) 4 d after initiation of GM1 infusion. Electrocorticographic recordings were monitored via indwelling cortical electrodes. Twenty-seven hours after soman administration, anesthetized rats were euthanized via transcardial perfusion with buffered paraformaldehyde. Brains were processed for hematoxylin and eosin (H&E), cresyl violet (CV), and acetylcholinesterase (AChE) histochemistry, and glial fibrillary acidic protein (GFAP) and microtubule-associated protein 2 (MAP2) immunohistochemistry. All soman-challenged rats not infused with GM1 (n = 14) developed status epilepticus (SE).

Acetylcholinesterase↗
PubMed1998

New reference allelic ladders to improve allelic designation in a multiplex STR system.

This paper reports the composition of a new reference allelic ladder mixture for use with a multiplex DNA profiling system consisting of six short tandem repeat loci. The loci included in this mixture are HUMTH01, D21S11, D18S51, D8S1179, HUMVWAF31/A, HUMFIBRA/FGA and an amelogenin sex test. Sequence analysis of individual ladder alleles was carried out and allelic designations made in accordance with the recommendations of the International Society of Forensic Haemogenetics (1992; 1994). A series of rare alleles which increase the range of alleles previously reported were identified. By including some of the rare alleles into the ladder marker system, we have significantly improved the ability to identify new alleles in unknown samples.

Alleles↗