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Biomedical subjects

C B Wright

Publications and source records attributed to C B Wright.

At least 19 recordsLinked to original sources

Eosinophilic vasculitis in an isolated central nervous system distribution.

BACKGROUND: Eosinophilic vasculitis has been described as part of the Churg-Strauss syndrome, but affects the central nervous system (CNS) in <10% of cases; presentation in an isolated CNS distribution is rare. We present a case of eosinophilic vasculitis isolated to the CNS. CASE REPORT: A 39-year-old woman with a history of migraine without aura presented to an institution (located in the borough of Queens, New York, USA; no academic affiliation) in an acute confusional state with concurrent headache and left-sided weakness and numbness. Laboratory evaluation showed increased cerebrospinal fluid (CSF) protein level, but an otherwise unremarkable serological investigation. Magnetic resonance imaging showed bifrontal polar gyral-enhancing brain lesions. Her symptoms resolved over 2 weeks without residual deficit. After 18 months, later the patient presented with similar symptoms and neuroradiological findings involving territories different from those in her first episode. Again, the CSF protein level was high. She had a raised C reactive protein level and erythrocyte sedimentation rate. Brain biopsy showed transmural, predominantly eosinophilic, inflammatory infiltrates of medium-sized leptomeningeal arteries without granulomas. She improved, without recurrence, when treated with a prolonged course of corticosteroids. CONCLUSIONS: To our knowledge, this is the first case of non-granulomatous eosinophilic vasculitis isolated to the CNS. No aetiology for this patient's primary CNS eosinophilic vasculitis has yet been identified. Spontaneous resolution and recurrence of her syndrome is an unusual feature of the typical CNS vasculitis and may suggest an environmental epitope with immune reaction as the cause.

Adult↗

Venous bypass of complicated stent placement for recurrent extracranial carotid occlusive disease.

Aim of the study was to to demonstrate a useful solution to carotid angioplasty and stent complications. A 67 year old male had uncomplicated left carotid endarterectomies in 1985 and 1986. A left distal common carotid angioplasty and stent in 1999 was complicated by stenosis. In 2000 a left common carotid bypass from the lower common carotid to the distal internal carotid well above the stent was performed, yielding retrograde filling of the external carotid, distal antegrade filling of the internal carotid, and widely patent vessels in subsequent Doppler studies. He is currently doing well clinically with no recurrent stenosis. In conclusion a second redo carotid operation was deferred in favor of angioplasty and stent, which had complications. Despite prior operations the only difficulty with the reoperation was obtaining control of the distal internal carotid above the stent. The strategy demonstrated here will be useful to correct complications of carotid angioplasty and stenting.

Aged↗

Diltiazem prophylaxis reduces incidence of atrial fibrillation after coronary artery bypass grafting.

AIM: To evaluate the prophylactic effect of diltiazem on the incidence of atrial arrhythmia (fibrillation and/or flutter) following coronary artery bypass grafting (CABG). Data were retrospectively gathered. METHODS: Patients undergoing elective CABG by one surgeon at one institution over a three-year period were considered for inclusion. Those selected were divided into 3 groups: A (patients placed on intravenous diltiazem intraoperatively, then converted to oral diltiazem upon initiation of oral intake); B (patients started on oral diltiazem upon initiation of oral intake without prior intravenous diltiazem); and C (patients receiving no diltiazem). A comparison of postoperative rates of atrial fibrillation was made between the 3 (demographically balanced) groups using logistic regression. RESULTS: Two hundred and eighty seven patients met inclusion criteria. The incidence of postoperative atrial fibrillation in the entire sample was 19.9% (57/287). Incidence of postoperative atrial fibrillation within each group was: A = 16.3% (22/135); B = 12.7% (7/55); C = 28.9% (28/97). Statistical significance was demonstrated for the following comparisons: A versus C (p = 0.0451) and B versus C (p = 0.0065). In an alternate model groups A and B were combined and compared to C (p = 0.0181). CONCLUSIONS: A lower incidence of atrial fibrillation following CABG was observed in patients treated prophylactically with diltiazem. Differences were statistically significant whether the drug was administered intravenously and orally (A) or only orally (B). Diltiazem, which has an established role in the management of atrial fibrillation, may prove to be well suited for prophylaxis due to low cost and relative safety.

Administration, Oral↗

Total homocysteine and cognition in a tri-ethnic cohort: the Northern Manhattan Study.

OBJECTIVE: Several studies implicate elevated homocysteine as a risk factor for dementia and cognitive decline, but most studies have involved subjects older than 55 years from homogeneous populations. The authors examined homocysteine and cognition in a tri-ethnic community sample 40 years and older. METHOD: The Northern Manhattan Study includes 3,298 stroke-free subjects. Of these 2,871 had baseline fasting total homocysteine (tHcy) levels and Mini-Mental State Examination (MMSE) scores available. The authors used multiple linear regression to examine the cross-sectional association between baseline tHcy levels and mean MMSE scores adjusting for sociodemographic and vascular risk factors. RESULTS: Homocysteine levels were related to age, renal function, and B12 deficiency. Those with B12 deficiency had tHcy levels five points higher (9.4 vs 14.4 nmol/L). Mean MMSE scores differed by age, sex, and race-ethnic group. Those with hypertension, diabetes, cardiac disease, and B12 deficiency had lower MMSE scores. In multivariate analyses, elevated tHcy was associated with lower mean MMSE scores for those older than 65 but not for those 40 to 64. Adjusting for B12 deficiency and sociodemographic factors the mean MMSE was 2.2 points lower for each unit increase in the log tHcy level (95% CI -3.6, -0.9). Adding vascular risk factors to the model did not attenuate this effect (mean MMSE -2.2 points; 95% CI -3.5, -0.9). CONCLUSIONS: Elevated homocysteine was independently associated with decreased cognition in subjects older than 65 in this tri-ethnic cohort, adjusting for sociodemographic and vascular risk factors.

Adult↗

Chlamydia pneumoniae in atherosclerotic carotid artery plaques: high prevalence among heavy smokers.

This study was designed to determine the prevalence of Chlamydia pneumoniae in carotid artery plaques. Although there have been numerous studies evaluating coronary plaques for this bacterium fewer studies have assessed noncoronary vasculature. In addition we wished to evaluate whether correlation exists between the presence of C. pneumoniae in carotid plaques and established risk factors for atherosclerosis. Sixty intact carotid artery plaques removed during surgery (carotid endarterectomy) were formalin-fixed and paraffin-embedded according to conventional techniques. These samples were evaluated by polymerase chain reaction analysis to detect presence of C. pneumoniae DNA. Results were tabulated and compared against established risk factors for atherosclerosis: diabetes, hypertension, hyperlipidemia, age, and smoking. Forty-two (70.0%) of the 60 plaques that were evaluated tested positive for the presence of C. pneumoniae DNA by polymerase chain reaction analysis. In the sample defined as being from heavy smokers (greater than 15-pack-year history) 33 (94.3%) of 35 plaques tested positive whereas two (5.7%) tested negative. This correlation demonstrated statistical significance (P = 1.36 x 10(-6), two-tailed Fisher exact test). Presence of C. pneumoniae in carotid plaques demonstrated no statistically significant correlation with diabetes, hypertension, or hyperlipidemia. Age as a risk factor was examined but not statistically evaluated because of the narrow range within our patient sample. Analysis of the data reveals that C. pneumoniae is present in large numbers of atheromatous plaques as is consistent with emerging data. What is interesting though is that 33 (94.3%) of the 35 smokers had plaques that tested positive for the bacterium as opposed to only nine (36.0%) of the 25 nonsmokers. Identification of specific populations exhibiting a high prevalence of C. pneumoniae may serve to focus future studies. Ongoing investigation will seek to determine whether C. pneumoniae plays an active role in the pathogenesis of atherosclerosis.

Age Factors↗

The advantages of the Harmonic Scalpel for the harvesting of radial arteries for coronary artery bypass.

BACKGROUND: Improvements in replacement vessel harvesting techniques and antispasmodic agents since the 1970s have led to a resurgence of interest in the radial artery (RA) as a conduit for coronary revascularization. METHODS: This randomized study compared the Ultra Cision Harmonic Scalpel (HS) (Ethicon Endo-Surgery, Inc., Cincinnati, OH) and the cold steel scalpel (CSS) for harvesting radial arteries to be used in coronary artery bypass grafting (CABG) procedures. Men and non-pregnant women, aged 21 to 79 years, with myocardial ischemia or coronary stenosis who were scheduled to undergo coronary bypass were enrolled in the study. RESULTS: Harvesting of the radial artery by the Harmonic Scalpel required a significantly lower number of clips to control bleeding. There was no significant difference between the times required to harvest the artery with either device. There were no complications, malfunctions, or serious adverse events associated with the use of either device. CONCLUSIONS: The Harmonic Scalpel provides excellent control of bleeding compared to the cold steel scalpel, and its use permits bleeding to be controlled without the need for potentially damaging electrocautery. No clinically significant adverse events were associated with the use of the Harmonic Scalpel.

Adult↗

Effects of valproic acid on beta-adrenergic receptors, G-proteins, and adenylyl cyclase in rat C6 glioma cells.

Valproic acid (VPA) is an anticonvulsant drug with demonstrated efficacy in the treatment of mania. In the present study, we found that chronic exposure of rat C6 glioma cells to VPA induces a coordinate decrease in multiple components of the beta-adrenergic receptor- (beta-AR) coupled cyclic adenosine 3'-5'monophosphate (cAMP) generating system. Chronic VPA decreased the number of beta-ARs in a time- and concentration-dependent manner; the decrease of beta-ARs was largely beta 1-AR selective and affected beta-ARs in both the high- and low-affinity states. Chronic VPA also significantly attenuated receptor- and postreceptor-stimulated cAMP production, [3H]forskolin binding sites, immunolabeling of G alpha s 45, and cholera toxin catalyzed ADP-ribosylation of G alpha s 52 and 45. Although the precise underlying mechanisms remain to be elucidated, such profound long-term changes in the functioning of this key signaling pathway may help explain the antimanic effects of chronic VPA treatment and are worthy of further study.

Adenylyl Cyclases↗

Attenuation of cyclic AMP production by carbamazepine.

The anticonvulsant carbamazepine is an effective treatment both for epilepsy and for bipolar affective disorder, but the molecular mechanism(s) underlying its therapeutic effects have not been identified. We have found that carbamazepine exerts significant inhibitory effects on the cyclic AMP (cAMP) generating system. Within the clinical therapeutic range (approximately 50 microM), carbamazepine inhibited both basal and forskolin-stimulated cAMP production, without having any significant effects on phosphodiesterase activity. Carbamazepine also exerted its inhibitory effects on the cAMP generating system in pertussis toxin-treated cells, suggesting that the action of carbamazepine was likely mediated through an inhibitory guanine nucleotide binding protein-independent mechanism. A forskolin affinity purification column was used to purify adenylyl cyclases from rat cerebral cortex, and we found that carbamazepine inhibited both basal and forskolin-stimulated activity of purified adenylyl cyclase. We also investigated the effects of carbamazepine on the levels of the transcription factor, cAMP response element binding protein in the phosphorylated (active) state, and found that carbamazepine significantly inhibited forskolin-induced phosphorylation of the cAMP response element binding protein. The data indicate that carbamazepine inhibits adenylyl cyclase activity as well as the downstream effects of activation of adenylyl cyclase.

1-Methyl-3-isobutylxanthine↗

Chronic sodium valproate selectively decreases protein kinase C alpha and epsilon in vitro.

Valproic acid (VPA) is a fatty acid antiepileptic with demonstrated antimanic properties, but the molecular mechanism or mechanisms underlying its therapeutic efficacy remain to be elucidated. In view of the increasing evidence demonstrating effects of the first-line antimanic drug, lithium, on protein kinase C (PKC), we investigated the effects of VPA on various aspects of this enzyme. Chronic exposure (6-7 days) of rat C6 glioma cells to "therapeutic" concentrations (0.6 mM) of VPA resulted in decreased PKC activity in both membrane and cytosolic fractions and increased the cytosol/membrane ratio of PKC activity. Western blot analysis revealed isozyme-selective decreases in the levels of PKC alpha and epsilon (but not delta or zeta) in both the membrane and cytosolic fractions after chronic VPA exposure; VPA added to reaction mixtures did not alter PKC activity or 3H-phorbol ester binding. Together, these data suggest that chronic VPA indirectly lowers the levels of specific isozymes of PKC in C6 cells. Given the pivotal role of PKC in regulating neuronal signal transduction and modulating intracellular cross-talk between neurotransmitter systems, the specific decreases in PKC alpha and epsilon may play a role in the antimanic effects of VPA.

Animals↗

Efficacy of carotid endarterectomy for asymptomatic carotid stenosis. The Veterans Affairs Cooperative Study Group.

BACKGROUND: The efficacy of carotid endarterectomy in patients with asymptomatic carotid stenosis has not been confirmed in randomized clinical trials, despite the widespread use of operative intervention in such patients. METHODS: We conducted a multicenter clinical trial at 11 Veterans Affairs medical centers to determine the effect of carotid endarterectomy on the combined incidence of transient ischemic attack, transient monocular blindness, and stroke. We studied 444 men with asymptomatic carotid stenosis shown arteriographically to reduce the diameter of the arterial lumen by 50 percent or more. The patients were randomly assigned to optimal medical treatment including antiplatelet medication (aspirin) plus carotid endarterectomy (the surgical group; 211 patients) or optimal medical treatment alone (the medical group; 233 patients). All the patients at each center were followed independently by a vascular surgeon and a neurologist for a mean of 47.9 months. RESULTS: The combined incidence of ipsilateral neurologic events was 8.0 percent in the surgical group and 20.6 percent in the medical group (P < 0.001), giving a relative risk (for the surgical group vs. the medical group) of 0.38 (95 percent confidence interval, 0.22 to 0.67). The incidence of ipsilateral stroke alone was 4.7 percent in the surgical group and 9.4 percent in the medical group. An analysis of stroke and death combined within the first 30 postoperative days showed no significant differences. Nor were there significant differences between groups in an analysis of all strokes and deaths (surgical, 41.2 percent; medical, 44.2 percent; relative risk, 0.92; 95 percent confidence interval, 0.69 to 1.22). Overall mortality, including postoperative deaths, was primarily due to coronary atherosclerosis. CONCLUSIONS: Carotid endarterectomy reduced the overall incidence of ipsilateral neurologic events in a selected group of male patients with asymptomatic carotid stenosis. We did not find a significant influence of carotid endarterectomy on the combined incidence of stroke and death, but because of the size of our sample, a modest effect could not be excluded.

Adult↗

Concomitant cardiac and pulmonary operation: the role of cardiopulmonary bypass.

To assess the safety and efficacy of concomitant pulmonary resection and cardiac operation requiring cardiopulmonary bypass, the records of 19 patients were reviewed. Eighteen patients (94.7%) presented with cardiac symptoms and were found to have pulmonary pathology of indeterminate etiology. Pulmonary resections were performed through a median sternotomy in all but 1 patient, who underwent posterolateral thoracotomy and right middle lobectomy after repositioning because dense adhesions prevented adequate dissection through the initial incision. A total of 24 resections were performed. Sixteen (66.7%) were performed on cardiopulmonary bypass. Six wedge resections (25.0%) were performed before bypass. Two lobectomies (8.3%) were performed after infusion of protamine sulfate. Nine patients (47.4%) had benign pathology, 7 (36.8%) had primary carcinoma, and 3 (15.8%) had metastatic disease. Bleeding complications occurred in 15.8% of patients (3/19). There was 1 perioperative death (5.3%), which was due to adult respiratory distress syndrome after intraoperative hemorrhage followed lobectomy for bullous disease. Another patient required lateral extension of the sternotomy during an episode of exsanguinating intraparenchymal pulmonary hemorrhage, which resulted in lobectomy, as well as costochondral and sternal osteomyelitis. A third patient required exploration for bleeding at the staple line. Postoperative complications occurred in 7 patients (36.8%) and were predominantly respiratory (5/7, 71.4%) (p = 0.006). The median postoperative hospitalization was 15 days. Although comparison of patients who underwent pulmonary resection during bypass with those who had resection either before heparinization or after protamine infusion showed no significant difference with respect to age, incidence of malignancy, operation performed, complications, postoperative hospitalization, or survival, this was probably due to the small number of patients in the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Use of plasma volume expanders in myocardial revascularisation.

The optimal solution for priming cardiopulmonary bypass machines and for postoperative resuscitation following myocardial revascularisation should be inexpensive, free of risk of transmitting disease, and free of other detrimental side effects. Colloid solutions are preferred over crystalloid solutions because of elevations in extracellular sodium and water that occur with cardiopulmonary bypass. Albumin, plasma protein solution, hetastarch (hydroxyethyl starch) and dextran are available for use if blood is not necessary and mediastinal blood is not available. Hetastarch is associated with a lower risk of bleeding and less risk of allergic reaction than dextran, and its cost is substantially less than that of albumin. However, high doses increase the risk of bleeding complications.

Colloids↗

Molecular surgery of the basement membrane by the argon laser.

Although the argon laser is used successfully to weld a number of different tissues, the underlying chemical and cellular mechanisms for this process are not precisely defined. Consequently, a biochemical model has been developed in vitro using the well-defined extracellular matrix from the murine Engelbreth-Holm-Swarm (EHS) sarcoma. Control and experimental samples of EHS basement membranes were irradiated with a Trimedyne argon laser at 500-3,000 Joules/cm2 at 0 degrees C. The samples were diluted into cold phosphate-buffered saline and allowed to gel at 35 degrees C. The time course of the gelation reaction was followed in a spectrophotometer at 360 nm. Irradiation reduced the absorbance 7.5-15% compared to controls and was independent of the dilution over a 10-fold range. Gelation was also measured by determining the amount of protein by the Bradford assay that could be collected by centrifugation at 10,000g for 10 minutes. Argon-irradiated samples had 30-40% less protein in the precipitate than the controls. The addition of 5 mM beta-mercaptoethanol to the EHS extract blocked the effect of the laser on the gelation reaction. In addition, when gelation was carried out in the absence of calcium and magnesium, there were no differences between laser-treated samples and controls. The basement membrane proteins were separated by electrophoresis through polyacrylamide gels under denaturing plus reducing or denaturing and non-reducing conditions. No differences in the polypeptide composition were noted between irradiated and control samples using either Coomassie- or silver-staining techniques.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Sternotomy infection: poor prediction by acute phase response and delayed hypersensitivity.

Two hundred twenty-one consecutive adult cardiac surgical patients were examined prospectively for nutritional protein state, acute phase protein response, and delayed hypersensitivity reaction in an attempt to identify patients at high risk for the development of sternal wound infection, which occurred in 6 patients (2.7%). There was no significant correlation between preoperative nutritional protein concentrations (retinol-binding protein, prealbumin, and transferrin) and acute phase protein levels (C-reactive protein, alpha 1-acid glycoprotein, and complements B and C3), nor a statistically significant relationship between nutritional state or acute phase protein response and the development of sternal infection. Preoperative complement C3 levels were elevated, however, in 80.0% of those in whom sternal infections developed compared with 30.6% of those with well-healed wounds. Similarly, postoperative concentrations of alpha 1-acid glycoprotein were elevated in 80.0% of those in whom sternal infections developed compared with 28.6% of those with well-healed wounds. There was no correlation between delayed hypersensitivity and the risk of sternal infection, nor between preoperative nutritional protein and acute phase protein values. Seventy-three percent of patients were anergic on postoperative day 2. Stepwise logistic regression showed that age, body weight, preoperative intensive care unit stay, repeat median sternotomy, internal mammary artery grafting, postoperative hemorrhage, and postoperative cardiac arrest correlated with the development of sternal infection, whereas transfusion requirement, reexploration for bleeding, and the operation performed did not. We conclude that routine delayed hypersensitivity testing is of no value in predicting high-risk cardiac surgical patients when the anergy battery is placed on the preoperative day. Although statistically insignificant, possibly due to the small number of patients in whom sternal infection developed in this study (type II error), a larger study might find preoperative complement C3 and post-operative alpha 1-acid glycoprotein levels to be predictive of patients at risk for the development of sternal wound infection. The final logistic model for the predicted risk 2%) of sternal wound infection is: PREDSWC = exp(EQ)/1 + exp(EQ) where EQ = (0.38 x age) + (0.24 x weight) + (5.42 x preop ICU) + (4.39 x redo) + (7.14 x IMA) + (4.49 x hemorrhage) + (8.81 x arrest) - 62.72, and where preop ICU, redo, hemorrhage, and arrest are defined as yes (1) or no (0), IMA-is defined as 0, 1, or 2, age is in years, and weight is in kilograms.

Acute-Phase Proteins↗

Surgical implications of sclerosing mediastinitis. A report of six cases and review of the literature.

Sclerosing mediastinitis is an uncommon disease associated with a multiplicity of clinical syndromes. The cause of this disorder is probably an abnormal fibroproliferative response to an inflammatory stimulus, most commonly a granulomatous infection secondary to Histoplasma capsulatum. The pathophysiology of this disease is predicated on the encasement of mediastinal vital organ structures within a dense fibrotic mass. This mass appears to emanate from an invasive chronic inflammatory process causing erosion as well as external compression of these structures. The following case reports illustrate the diversity of this disease entity, representing a patient population from the Ohio River Valley, endemic for histoplasmosis. The purpose of this report is to elucidate the various clinical manifestations of sclerosing mediastinitis and to correlate the pathologic process with a rational approach to treatment.

Adult↗

The effects of cardiopulmonary bypass and cold cardioplegia on coronary flow velocity and the reactive hyperemic response in patients and dogs.

In normal coronary arteries, reactive hyperemic responses to a 20-second occlusion, an index of coronary reserve, usually demonstrate a peak-to-resting flow velocity ratio of 4:1 or more. Most intraoperative studies that have assessed reactive hyperemic responses in bypassed vessels have reported peak-to-resting flow velocity ratios of 2:1 or less following a 20-second occlusion. These decreased reactive hyperemic responses could be due to coronary vasodilatation after cardiopulmonary bypass or to an inadequate physiological result of the surgical procedure. In 14 patients with angiographically normal coronary arteries, the peak-to-resting flow velocity ratio following a 20-second coronary occlusion decreased significantly (p less than 0.05) from 4.4 +/- 0.2 (mean +/- standard error) before bypass to 3.0 +/- 0.3 after bypass. In a similar dog model, the peak-to-resting flow velocity ratio decreased by 36 to 52% during the first hour following one hour of cardiopulmonary bypass and cardioplegia. During the same period, left ventricular perfusion increased 21 to 30%, mean arterial pressure and coronary vascular resistance decreased, and myocardial oxygen consumption was unchanged. In a second group of dogs studied for the effects of duration (200 to 240 minutes) of anesthesia and thoracotomy alone, peak-to-resting flow velocity ratio was significantly lower. These clinical and experimental studies suggest that major coronary vasodilatation occurs early following cardiopulmonary bypass and cold cardioplegia, and may contribute to the blunted coronary reactive hyperemic responses reported during this time. Consequently, an intraoperative peak-to-resting flow velocity ratio of 3:1 for bypassed coronary arteries may represent an excellent physiological result.

Adolescent↗

A modified technique for use of the intraluminal valve cutter in in situ saphenous vein grafts.

A modified technique for the use of the disposable intraluminal valve cutter in the performance of in situ saphenous vein arterial bypass grafts is presented. The technique results in a more physiologic dilatation of the vein and can be expeditiously performed with minimal intimal trauma to the vein graft. Long incisions necessary to expose the entire vein with the use of other techniques can be avoided, thereby decreasing the potential for wound healing problems commonly associated with vascular reconstruction in ischemic limbs.

Catheterization↗