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Biomedical subjects

C D Smith

Publications and source records attributed to C D Smith.

At least 109 records · Page 6Linked to original sources
PubMed1998

Minimal increase in gut-mucosal interleukin-6 during laparoscopy.

BACKGROUND: The gut clearly plays a significant role in postoperative recovery. Other investigators have shown an increase in gut-mucosal cytokines in septicemia and burn models. We tested the effects of laparotomy and laparoscopy on gut-mucosal IL-6 production. METHODS: A/J mice were randomized to three groups: control, laparotomy plus bowel manipulation (OBM), and laparoscopy plus bowel manipulation (LBM). Serum and gut-mucosal samples obtained at 4 and 8 h after surgery were analyzed for IL-6. RESULTS: We found that OBM is associated with increased serum and gut-mucosal IL-6 at both 4 and 8 h after surgery. In contrast, LBM showed a blunted response in serum IL-6 and no change in gut-mucosal IL-6 at both time intervals. CONCLUSIONS: We conclude that laparoscopy minimizes trauma to the peritoneal environment, thereby decreasing the gut's inflammatory response to operation. This differential response of the gut may partially explain the preservation of gut function following laparoscopy.

Animals↗
PubMed1998

Tumor response, mucosal reactions and late effects after conventional and hyperfractionated radiotherapy.

BACKGROUND: Relationships between normal tissue reactions and tumor response to radiotherapy have generally been investigated in retrospective studies, with the attendant difficulties such as different times of treatment and lack of standard scales for scoring of normal tissue reactions. This study analyses the correlation between normal tissue reactions and tumor response in a randomized trial of hyperfractionation versus conventional radiotherapy. MATERIALS AND METHODS: EORTC trial 22791, which accrued 325 T2-3, N0-1 and M0 oropharynx squamous cell carcinomas, compared conventional radiotherapy (70 Gy in 7 weeks) to a hyperfractionated regime (two daily irradiations of 1.15 Gy up to 80.5 Gy in 7 weeks). Acute and late toxicities were assessed according to the RTOG/EORTC scales. The variables were tumor regression at treatment completion, tumor control for unlimited follow-up, severity of acute mucosal reactions (grade of the peak reaction, time to onset of grade 2 mucositis, or duration of acute reactions of grade 3) and severity of late effects in normal tissues (late ulceration, cervical edema secondary to lymphatic drainage damage, late muscular fibrosis, or late mucosal necrosis as consequential damage). Kendall's rank correlation was used to assess the levels of significance of the correlation. The 95% confidence interval (95% CI) was calculated for each correlation tau-b coefficient. RESULTS: Irradiation doses and overall treatment times were consistent between the treatment arms. The time to onset of patchy mucosal reactions was inversely correlated to tumor regression at treatment completion in the hyperfractionated arm (arm 2) but not in the conventional fractionation arm (arm 1). The other significant correlations were restricted to the following pairs of end-points and patient subgroups: acute mucositis of grade 3 versus tumor regression at the end of treatment in arm 2 for T2 tumors, late ulceration versus tumor control in arm 2 and acute mucosal reactions versus late effects in normal tissues in arm 2 for T3 tumors. By and large, the 95% CIs for Kendall's tau-b included zero and did not include 0.5, an indication that the comparison had sufficient power to detect a difference, if indeed one existed. CONCLUSIONS: These results do not represent clinical evidence strong enough to demonstrate that individual differences in sensitivity influence the response of tumors to radiation.

Carcinoma, Squamous Cell↗
PubMed1998

Tolyporphins J and K, two further porphinoid metabolites from the cyanobacterium Tolypothrix nodosa.

Two new porphinoids, tolyporphins J (1) and K (2), have been isolated from the terrestrial cyanobacterium, Tolypothrix nodosa (HT-58-2) and identified by NMR and mass spectral analysis. The activities of tolyporphins J and K in cell sensitization and drug accumulation assays for multidrug resistance (MDR) reversal were compared with those of tolyporphin A. Unusual NMR spectroscopic shifts were observed for tolyporphin J (1) in CDCl3.

Antibiotics, Antineoplastic↗
PubMed1998

Preoperative perfusion of bypassed ileum does not improve postoperative function.

This study evaluated whether twice daily isotonic perfusion of the bypassed ileum for six weeks would enhance its motor activity and its absorption of fluids, electrolytes, and vitamin B12. The study also determined if patients undergoing perfusion had improved bowel function and decreased hospital stay after ileostomy closure. Following proctocolectomy, ileal pouch-anal canal anastomosis, and diverting loop ileostomy, six patients self-infused an isotonic solution (sucrose and sodium chloride) into the bypassed ileum twice daily, while seven patients did not (controls). Two months following proctocolectomy, and just prior to ileostomy closure, a manometric catheter assembly was placed into the unused distal ileum via the stoma and the distal ileum perfused with an isotonic sodium chloride solution for 3 hr during fasting and 3 hr after a meal. Absorption was measured, single and clustered pressure waves were identified, and a motility index was calculated. Water absorption, motility index, and cluster parameters did not improve in perfused patients compared to controls during fasting or after a meal, nor did perfused patients have improved vitamin B12 absorption. The perfused patients also did no better clinically following ileostomy takedown; the onset of bowel movements, their frequency, time to tolerate a diet, and hospital stay were similar to controls. We conclude that six weeks of twice daily isotonic perfusion did not improve motor activity or water, electrolyte, and vitamin B12 absorption in the bypassed distal ileum after proctocolectomy, ileal pouch-anal canal anastomosis, and loop ileostomy. The perfusion also did not improve bowel function after ileostomy takedown.

Chronic Disease↗
PubMed1998

A long-term study of hydroxychloroquine withdrawal on exacerbations in systemic lupus erythematosus. The Canadian Hydroxychloroquine Study Group.

The ability of antimalarials to moderate severe disease activity in systemic lupus erythematosus (SLE) is plausible but undemonstrated. We evaluated the long-term effectiveness of maintaining treatment with hydroxychloroquine sulphate (HCQ) to prevent major flares in quiescent SLE. Forty-seven patients with quiescent SLE who had been randomized to take HCQ (n = 25) or placebo (n = 22) as part of a 24-week withdrawal trial were evaluated for an additional 3 years. The primary outcome was time to a major flare of SLE which resulted in either the institution of or an increase in the current dosage of prednisone of 10 mg/day or more, or institution of therapy with immunosuppressive agents. Secondary outcomes included the specific subtype of these major flares (glomerulonephritis, vasculitis or other) and hospitalization for an exacerbation of SLE. An intent-to-treat analysis was conducted. Over the 42 months of study, 11 of 22 (50%) patients randomized initially to placebo, and seven of 25 (28%) patients randomized to continue treatment experienced a major flare. The relative risk of major flare for those randomized to continue HCQ compared with controls was 0.43 (95% CI: 0.17, 1.12). The relative risks for subtypes of flares were 0.26 (95% CI: 0.03, 2.54) for nephritis, 0.51 (95% CI: 0.09, 3.08) for vasculitis and 0.65 (95% CI: 0.17, 2.41) for flares characterized by other symptoms. The relative risk of hospitalization for major flare for patients randomized to continue hydroxychloroquine was 0.58 (95% CI: 0.13, 2.60). While the results are not statistically significant, they are compatible with the clinical belief that HCQ has a long-term protective effect against major disease flares in SLE and suggest that on average, HCQ use reduces major flares by 57% (95% CI: 83% reduction to 12% increase).

Adult↗
PubMed1998

Neural lesions in the rat and their relationship to EEG delta activity following seizures induced by the nerve agent soman.

This study describes the neural structures damaged following exposure to the nerve agent soman, shows there are time-dependent differences in the extent of damage in certain structures, and relates seizure-induced increases in delta band (0-3.5 Hz) electroencephalographic (EEG) activity with severity of subsequent neuropathology. Rats, instrumented to record cortical EEG activity, were pretreated with the oxime HI-6 (125 mg/kg, i.p.) and then challenged with soman (180 ug/kg, s.c.). All animals developed continuous epileptiform seizures that lasted in excess of 4 hr. Groups of animals were perfused 1, 3, 10 or 30 days following exposure. Paraffin-embedded brains were stained with hematoxylin and eosin; thirty-four neural structures were examined and scored for neural damage. All cortical areas sustained damage, with piriform and perirhinal cortices exhibiting the most severe. Subcortical limbic areas (amygdala, amygdala-piriform transition zone, hippocampus, claustrum) and various thalamic nuclei were most consistently and severely damaged in all animals regardless of survival time. Brainstem structures, cerebellum, spinal cord, and other motor output nuclei were never damaged. It was found that some structures were rated as more severely damaged when evaluated at shorter survival times. Severity of neural damage was related to high levels of EEG delta power recorded 24 hr after exposure; power during the acute seizure or 24 hr body weight loss did not predict lesion severity. Sections between AP -0.8 to -4.8 contain cortical and subcortical structures that can be readily and reproducibly evaluated for brain damage.

Animals↗
PubMed1997

Microfilament depletion and circumvention of multiple drug resistance by sphinxolides.

Sphinxolides, a newly described family of cytotoxins from the New Caledonian sponge Neosiphonia superstes, bear structural resemblance to scytophycins. We now demonstrate that the cytotoxicity of sphinxolides is associated with cell cycle arrest in G2-M and induction of apoptosis. Like scytophycins and cytochalasins, sphinxolides caused rapid loss of microfilaments in cultured cells, without affecting microtubule organization. Microfilament reassembly was very slow after removal of the sphinxolide, consistent with the slow recovery of cellular proliferation. Sphinxolides potently inhibited actin polymerization in vitro and the microfilament-dependent ATPase activity of purified actomyosin, indicating a direct effect on actin. Importantly, sphinxolides were equally cytotoxic toward MCF-7 human breast carcinoma cells and a subline which overexpresses P-glycoprotein (MCF-7/ADR). Similarly, overexpression of the multidrug resistance-associated protein MRP by HL-60 cells did not confer resistance to the sphinxolides. These studies demonstrate that sphinxolides are potent new antimicrofilament compounds that circumvent multidrug resistance mediated by overexpression of either P-glycoprotein or MRP. Therefore, these agents may be useful in the treatment of drug-resistant tumors.

Actin Cytoskeleton↗
PubMed1997

Preliminary crystallographic study on a low molecular weight form of bacterial plasminogen activator staphylokinase.

Staphylokinase, a 17 kDa protein, produced by certain strains of Staphylococcus aureus functions as a fibrin-specific plasminogen activator. During its interaction with plasminogen, staphylokinase is converted into a low molecular weight form by loss of ten amino-terminal residues. This low molecular weight form of recombinant staphylokinase has been crystallized using the hanging-drop vapor-diffusion technique with polyethylene glycol 4000 as precipitant. Crystals belong to the orthorhombic space group C222(1) with unit-cell dimensions a = 43.78, b = 59.86 and c = 103.25 A and one molecule in the asymmetric unit. These crystals diffract to about 2.4 A resolution.

Journal Article↗
PubMed1997

The expression of creatine kinase isoenzymes in neocortex of patients with neurodegenerative disorders: Alzheimer's and Pick's disease.

Creatine kinase (CK) activity was found decreased in the brains of patients with Alzheimer's disease (AD) and Pick's disease (PD). However, the decrease of total CK activity in AD was more pronounced than in PD. Analysis of the activity of two CK isoforms, BCK and ubiquitous mitochondrial CK, demonstrated that the decrease of total CK activity in AD and PD was related to the decrease of BCK activity. The decline of CK activity both in AD and PD correlated well with the decline of the content of immunoreactive BCK in brain extracts. The BCK mRNA level in AD and PD was not significantly different from control patients and could not be the primary reason for decreases in CK content and activity. The decreased level of BCK in AD and PD brains might be caused by posttranscriptional events, which could affect the translation of BCK mRNA and/or lead to the inactivation and degradation of the enzyme. Because CK is sensitive to oxidative modification, it is possible that the changes observed in this study result from free radical damage.

Aged↗
PubMed1997

Intraoperative events common to videoscopic preperitoneal mesh inguinal herniorrhaphy.

BACKGROUND: Videoscopic preperitoneal mesh (VPM) inguinal herniorrhaphy avoids the entry into the abdominal cavity, which is necessary with other videoscopic techniques. Despite this advantage, surgeons have been slow to adopt this technique. We reviewed our experience with VPM inguinal herniorrhaphy, specifically investigating the technical aspects of this approach. METHODS: Data were collected prospectively. Operative notes were reviewed retrospectively detailing intraoperative events not "typical" with the VPM technique. RESULTS: One hundred consecutive patients undergoing VPM repair of 127 hernias were studied. The repair was completed in all but 2 patients. Mean operating time was 120 minutes (60 to 146). In 36 repairs there were 59 intraoperative "events" requiring specific maneuvers to correct. Events identified were the need for transection of the hernia sac, creation and repair of a peritoneal tear, and need to divide the inferior epigastric vessels. No complications related to these events occurred. When events occurred, operative times were significantly longer (146+/-45 versus 83+/-23 minutes; P <0.05). CONCLUSION: Intraoperative events are common with VPM herniorrhaphy. These events significantly prolong operating time. A surgeon's lack of familiarity with such events and how to deal with them may in part explain the reluctance to widely apply the VPM technique.

Female↗
PubMed1997

Save the child's esophagus, Part II: Colic patch repair.

PURPOSE: In a previous report, the authors documented the procedures necessary to regain esophageal continuity in infants who had massive disruption of the suture line following esophagoplasty. As a corollary, this study shows the feasibility of preserving the esophagus in older children by using an esophageal patch. METHODS: Fifteen children ranging in age from 8 months to 16 years at the time of surgery had repair of esophageal strictures or tracheoesophageal fistulae by the use of a vascularized patch rather than esophageal resection and interposition with colon or stomach. The technique of "colonic-patch oesophagoplasty" was described by Hecker and Hollman in 1975. From 1976 to 1995, the authors have used a modification of their procedure in 14 children, and in one patient an intercostal muscle flap was interposed. The technique consists of esophagotomy through the area of stricture with application of a vascularized patch of colon to the resulting defect. RESULTS: Ten of the patients were boys and four were girls with an additional girl considered for the procedure at 8 months of age. However, during surgery, an intercostal muscle flap interposition was used. Eight children had esophageal stricture caused by lye ingestion; two from anastomotic stricture; two from gastroesophageal reflux; two from recurrent tracheoesophageal fistula; and one from long-term nasogastric intubation. Follow-up showed excellent results in nine patients who had the colic patch operation. All had good swallowing. A tenth patient, the child with the vascularized intercostal muscle flap, is currently eating a regular diet but it has only been 4 months since the operation. However, one of these excellent patients continues to have a small focus of Barrett's esophagus and another one was killed in an automobile accident one year after operation. Three children have good results but with occasional difficulty in swallowing boluses of meat or with continuing reflux. Two patients had poor results and both have undergone reoperation. In one of these children with Down's syndrome and diabetes, the colic patch worked well for 6 years but because of continuing reflux, distal esophageal scarring and obstruction eventually ensued. After reoperation for distal esophageal resection and colic interposition, the patient died of pulmonary failure. The second child with poor results has recently undergone reoperation to extend the esophagotomy through the distal scarred esophagus and to revise the colic patch. CONCLUSION: The use of a vascular colic patch for treatment of severe esophageal strictures is a viable alternative to esophageal resection and interposition. However, patients with continuing reflux or Barrett's esophagus, or both, may progress with distal esophageal scarring and obstruction and subsequent dilation of the patch. Those patients will require reoperation.

Adolescent↗
PubMed1997

Crystallization and preliminary cryogenic X-ray diffraction analyses of protein L-isoaspartyl O-methyltransferase from human fetal brain.

Recombinant human fetal brain protein L-isoaspartyl O-methyltransferase, EC 2.1.1.77, was crystallized in PEG 8000 with adenosine homocysteine by a macroseeding technique. The space group was P2(1) with a = 47.4 A, b = 53.9 A, c = 48.7 A and beta = 116.4 degrees for cryofrozen crystals at 90 K. The crystals diffracted to 2.1 A and have one molecule per asymmetric unit.

Brain Chemistry↗
PubMed1996

Mechanism of action cryptophycin. Interaction with the Vinca alkaloid domain of tubulin.

Cryptophycin is a potent antitumor agent that depletes microtubules in intact cells, including cells with the multidrug resistance phenotype. To determine the mechanism of action of cryptophycin, its effects on tubulin function in vitro were analyzed. Cryptophycin reduced the in vitro polymerization of bovine brain microtubules by 50% at a drug:tubulin ratio of 0.1. Cryptophycin did not alter the critical concentration of tubulin required for polymerization, but instead caused substoichiometric reductions in the amount of tubulin that was competent for assembly. Consistent with its persistent effects on intact cells, cryptophycin-treated microtubule protein remained polymerization-defective even after cryptophycin was reduced to sub-inhibitory concentrations. The effects of cryptophycin were not due to denaturation of tubulin and were associated with the accumulation of rings of microtubule protein. The site of cryptophycin interaction with tubulin was examined using functional and competitive binding assays. Cryptophycin blocked the formation of vinblastine-tubulin paracrystals in intact cells and suppressed vinblastine-induced tubulin aggregation in vitro. Cryptophycin inhibited the binding of [3H]vinblastine and the hydrolysis of [gamma32P]GTP by isolated tubulin, but did not block the binding of colchicine. These results indicate that cryptophycin disrupts the Vinca alkaloid site of tubulin; however, the molecular details of this interaction are distinct from those of other antimitotic drugs.

Animals↗
PubMed1996

Cortical activation in confrontation naming.

Functional magnetic resonance imaging was used to detect cortical activation in the right and left perisylvian cortex of seven young adult right-handed volunteers in response to a letter fluency task and to a visual naming task using standardized line drawings. Both letter fluency and visual naming activated left dorsolateral prefrontal cortex (Brodmann's areas 6, 9, 44 and 45). Only visual naming activated area 37 (a cortical region with strong connections to visual association areas), visual association area 19, and areas 39 and 21 previously shown to activate with auditory semantic tasks. This study supports a role for area 37 as participant in a visual lexicosemantic processing network which may otherwise overlap the auditorysemantic network.

Adult↗
PubMed1996

Aortoesophageal fistula and double aortic arch: two important points in management.

Two children with double aortic arch and aortoesophageal fistula (AEF) are reported to warn of this lethal complication of double aortic arch and to stress important points in the diagnosis and management. A review of the records of 30 children with double aortic arch disclosed two patients who had AEF. The first patient had respiratory distress and repair of a vascular ring (double aortic arch) at 5 weeks of age. At 9 weeks of age, because of difficulty with tracheal extubation, aortopexy was performed. Ten days later, profuse upper gastrointestinal bleeding required control by a Sengstaken-Blakemore (SB) tube. Thoracotomy and repair AEF was accomplished successfully under cardiopulmonary bypass. The second patient had hepatomegaly and Pseudomonas sepsis. Endotracheal and nasogastric intubation was necessary, and subsequently the double aortic arch was demonstrated by magnetic resonance imaging (MRI). On the 48th day of hospitalization, life-threatening upper gastrointestinal hemorrhage required insertion of an SB tube. Cardiopulmonary bypass allowed successful repair of the AEF. Both children are alive, after 3 and 2 years (respectively). These patients demonstrate that AEF must be diagnosed clinically (no imaging technique is effective); its history and physical presentation are typical. The SB tube is effective for controlling the hemorrhage until cardiopulmonary bypass can be performed to allow repair.

Airway Obstruction↗