The uncertainties surrounding carotid endarterectomy.
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Age Factors↗
Biomedical subjects
J T Robertson
Publications and source records attributed to J T Robertson.
Evidence for the involvement of a potential second tumor suppressor gene on chromosome 17 distinct from p53 in malignant astrocytomas.
Molecular analysis of malignant astrocytomas demonstrated three distinct groups of tumors with chromosome 17p abnormalities, which include (a) deletion of the p53 locus (17p13.1) and mutations in the remaining allele, (b) deletion of the p53 locus but no detectable mutations in the remaining allele, and (c) deletions not including the p53 locus but mutations in one of the alleles. Furthermore, deletion mapping analysis demonstrated allelic loss of genes distal to D17S28/D17S5 markers (17p13.3) in group C tumors. The loss of heterozygosity of genes on chromosome 17 without detectable mutation (group B) or deletion (group C) in the p53 gene implies the presence of a second tumor suppressor gene in the telomeric region of 17p, the homozygous functional inactivation of which may play a role, either alone or in conjunction with p53, in the initiation and/or progression of astrocytic neoplasms.
Base Sequence↗
Amplification and/or overexpression of platelet-derived growth factor receptors and epidermal growth factor receptor in human glial tumors.
Analysis of genomic organization and expression of platelet-derived growth factor receptors (PDGFR) and epidermal growth factor receptor (EGFR) in human malignant gliomas showed amplification and overexpression of both receptors in distinct subsets of tumors. Amplification of the alpha PDGFR was detected in 4 of 50 glioblastomas (8%). EGFR was amplified in 9 of the 50 tumors (18%). Western blot analysis showed elevated expression of alpha PDGFR and EGFR proteins in 4 (24%) and 3 (18%), respectively, of 17 tumor specimens analyzed. Increased production of alpha PDGFR as well as EGFR proteins was observed in the presence or absence of gene amplification. Three of the 4 tumors with elevated levels of alpha PDGFR also overexpressed the beta PDGFR, which was present as a single copy gene in all 50 tumors analyzed. Our findings suggest that the amplification and/or overexpression either of EGFR or of the alpha PDGFR along with the coordinate overexpression of the beta PDGFR can contribute to the malignant phenotype of distinct subsets of human glioblastoma.
Blotting, Western↗
Uterine torsion and uterine tear in a mare.
A 15-year-old Standard-bred mare was examined because of signs of abdominal discomfort in late gestation. Palpation per rectum revealed tight broad ligaments above and below the uterus, with the right broad ligament running across the top of the uterine body down toward the left, ventral side of the abdomen. A diagnosis of counterclockwise uterine torsion was made and surgical correction was approached via a left, flank laparotomy with the horse standing. The uterus was repositioned and a uterine tear encompassing 180 degrees of the uterine surface was found in the lateral, uterine body just cranial to the cervix. A live colt was delivered vaginally after uterine repositioning and the laparotomy incision was closed. The uterine tear was then repaired via a blind, vaginal approach. The mare was discharged 10 days after surgery. Repair per vaginum of a uterine tear is presented as an alternative treatment in cases for which the tear is recent, abdominal contamination is minimal, and the tear is easily accessible from the vaginal approach.
Animals↗
Cystic structures in the guttural pouch (auditory tube diverticulum) of two horses.
Two horses were examined for compression of the pharynx from the dorsal pharyngeal wall. Neither horse had a patent opening of 1 of the guttural pouches. Radiography of the guttural pouch region revealed a retropharyngeal opacity that occluded 1 guttural pouch. Organisms were not isolated on bacteriologic culture of fluid obtained from the affected guttural pouch. Surgical exploration of the guttural pouch revealed the lining to be easily removeable by blunt dissection in 1 horse; however, the lining was more firmly attached and removal was not attempted in the second horse. A fenestration between the normal and affected guttural pouch was created in both horses to allow for drainage. The etiopathogenesis of the cyst in the guttural pouches is unknown.
Animals↗
Assessment of lumiaggregometry for research and clinical laboratories.
Platelet aggregometry is often used to help diagnose storage pool disease (SPD-reduced amounts of granule nucleotides) and release defects (abnormal release of granule nucleotides). The general assumption that normal aggregation patterns are sufficient to rule out the diagnosis of one of these disorders has been invalidated by the recent publication of two papers describing patients with clinical bleeding, prolonged bleeding times and normal aggregation patterns in spite of defective release. The lumiaggregometer provides a tool for measuring platelet release and aggregation simultaneously. This paper presents a standardized, reproducible method for the use of the lumiaggregometer based on a "standard curve". Data obtained during the development of the procedure are presented including normal ranges of release at different concentrations of agonists, release measured in intrinsic disorders as well as in patients on aspirin, and values for release relative to varying platelet counts. A monoclonal antibody (anti-p24/CD9; MAb7) which activates platelets similarly to thrombin and may be a useful reagent for distinguishing SPD and release defects is also introduced.
Adenosine Triphosphate↗
Subcutaneous emphysema from an axillary wound that resulted in pneumomediastinum and bilateral pneumothorax in a horse.
A 5-year-old Thoroughbred gelding was examined because of a small axillary wound sustained 5 days earlier and had resulted in extensive subcutaneous emphysema. Three days after admission, the horse's respiratory rate had increased to 72 breaths/min, and the horse appeared anxious and distressed. Thoracic radiography revealed pneumomediastinum and severe bilateral pneumothorax. Tube thoracostomy was performed on both hemithoraxes. The drains were connected to one-way suction valves and suction devices to decompress the thorax. A nasopharyngeal catheter was inserted, and oxygen insufflation was started. Cross ties were placed on the horse to limit movement, and the wound was packed. The horse improved within 30 minutes after initiating treatment. The horse was released 15 days after the development of pneumothorax, at which time the pneumothorax had resolved, the wound was no longer open, and the subcutaneous emphysema had greatly decreased. Although subcutaneous emphysema is usually regarded as a temporary cosmetic disfigurement, it can lead to serious complications such as pneumothorax. This case demonstrates that subcutaneous emphysema can lead to a life-threatening pneumothorax if the pressure is great enough to migrate through the mediastinum and into the pleural cavity. Horses with subcutaneous emphysema should be kept in confinement and monitored for the development of pneumothorax.
Animals↗
Constrictive pericarditis in a mare: attempted treatment by partial pericardiectomy.
Chronic constrictive pericarditis was diagnosed in a 6-year-old Thoroughbred mare based on the clinical findings of right congestive heart failure, hyperechoic pericardium without pericardial effusion, and a dip-and-plateau shape of the right ventricular pressure curve with equilibration of the diastolic pressures in all cardiac chambers. Treatment was attempted by partial pericardiectomy using a right lateral thoracotomy approach. Because of severe epicardial involvement recurrence of the constrictive pathology was noted 6 weeks after the surgical procedure. However, in selected cases in which the disease process is limited to the pericardium, partial pericardiectomy may offer a mode of therapy in horses suffering from constrictive pericarditis.
Animals↗
Symptomatic carotid artery stenosis: a solvable problem. North American Symptomatic carotid Endarterectomy Trial.
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Carotid Stenosis↗
A randomized comparison of intra-arterial versus intravenous BCNU, with or without intravenous 5-fluorouracil, for newly diagnosed patients with malignant glioma.
This Phase III trial tested the efficacy and safety of intra-arterial 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) for the treatment of newly resected malignant glioma, comparing intra-arterial BCNU and intravenous BCNU (200 mg/sq m every 8 weeks), each regimen without or with intravenous 5-fluorouracil (1 gm/sq m three times daily given 2 weeks after BCNU). All patients also received radiation therapy. A total of 505 patients were randomly assigned within the study. Fifty-seven patients were excluded, primarily because of neuropathology error, and the remaining 448 patients constituted the Valid Study Group. Of the total 505 patients, 190 patients could not receive intra-arterial BCNU and 315 patients were randomly assigned to receive intra-arterial (167 patients) and intravenous (148 patients) BCNU. Actuarial analysis (log-rank) demonstrated reduced survival for the intra-arterial group (p = 0.03). Serious toxicity was observed in the intra-arterial group; 16 patients (9.5%) developed irreversible encephalopathy with computerized tomography evidence of cerebral edema, and 26 patients (15.5%) developed visual loss ipsilateral to the infused carotid artery. Administration of 5-fluorouracil did not influence survival. The survival rate between the intravenous and the intra-arterial BCNU patients with glioblastoma multiforme did not differ, but was worse for intra-arterial BCNU patients with anaplastic astrocytoma than for those receiving intravenous BCNU (p = 0.002). Neuropathologically, intra-arterial BCNU produced white matter necrosis. It is concluded that intra-arterial BCNU is neither safe nor effective in prolonging survival when administered by the methods used in this study of newly diagnosed patients with malignant glioma.
Adolescent↗
Clonal composition of glioblastoma multiforme.
Glioblastoma multiforme, the most common and most lethal primary central nervous system neoplasm, is noted for its phenotypic and biological heterogeneity. This heterogeneity may result from genetic alterations accumulated by a single transformed astrocyte as it evolves into a monoclonal tumor. Alternatively, it may be attributed to the presence of multiple biologically and genetically distinct astrocytic populations within a polyclonal tumor. To address the issue of clonal composition of glioblastoma multiforme the authors used two independent approaches: analysis of X-chromosome inactivation and analysis of chromosomes 10 and 17 for tumor-specific somatic deletions. The analysis included 10 tumors from nine female patients with glioblastoma multiforme (eight primary and two recurrent tumors), who were heterozygous at either of two X-chromosome genes (hypoxanthine phosphoribosyl-transferase or phosphoglycerate kinase). Nine glioblastomas multiforme demonstrated a monoclonal pattern on X-chromosome analysis; contamination with normal tissue obscured the analysis in one tumor. Somatic deletions on chromosomes 10 and/or 17 occurred in nine tumors, supporting a monoclonal composition for these tumors. These data suggest that glioblastoma multiforme is a monoclonal neoplasm, derived from the clonal expansion of a single transformed astrocyte that has, as a fundamental step in tumorigenesis, sustained a critical genetic alteration on chromosome 10 and/or 17.
Brain Neoplasms↗
The AANS: the national and international organization for neurological surgery.
The President of the American Association of Neurological Surgeons (AANS) validates the AANS as the national neurosurgical organization. He describes improved management of major committees of neurological surgery by the Joint Officers of the AANS and the Congress of Neurological Surgeons. A strong argument and proclamation are presented to expand the international role of the former Harvey Cushing Society.
Neurosurgery↗
Carotid endarterectomy: practice guidelines. Report of the Ad Hoc Committee to the Joint Council of the Society for Vascular Surgery and the North American Chapter of the International Society for Cardiovascular Surgery.
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Brain Ischemia↗
Additional diagnostic procedures.
This article reviews recent diagnostic procedures that have arisen over the last 10 years. Videoendoscopy of horses on a high-speed treadmill allows observation of some of the changes that take place in a horse's airway during exercise. Measurements of upper airway airflows and transupper airway pressure, the use of an esophageal balloon and a Ventigraph to measure changes in pleural pressure, and pulmonary function testing are new techniques that aid the researcher in understanding the mechanics and pathologic characteristics of airway diseases and help the practitioner in assessing the severity of a problem, measuring response to therapy, and accurately determining a prognosis.
Animals↗
Effect of neurotrauma on hepatic drug clearance.
Lorazepam, antipyrine, and indocyanine green were administered to 10 patients with severe head injuries as marker substrates of hepatic glucuronidation, oxidation, and hepatic blood flow, respectively. Pharmacokinetic parameter estimates were determined at baseline (20 to 80 hours after injury) and up to three additional times thereafter (study days 4, 7, and 14). Antipyrine clearance was increased significantly from baseline (0.50 +/- 0.31 ml/min/kg) on study days 4, 7, and 14 (p less than 0.0001). Increases in antipyrine clearance from baseline to the last study day were observed in all study patients ranging from 14% to 207%. A significant increase was also observed in lorazepam clearance on study day 14 relative to baseline (1.39 +/- 0.56 ml/min/kg) (p less than 0.005). Increases in lorazepam clearance occurred in seven of nine patients over time ranging from 9% to 130%. The unbound fraction of lorazepam did not change significantly over the study period. Likewise, no significant change was observed in the clearance of indocyanine green over time. Antipyrine clearance and alpha 1-acid glycoprotein (r = 0.41), and lorazepam clearance and C-reactive protein (r = -0.38) were significantly correlated (p less than 0.05). Similarly, antipyrine and lorazepam clearances were significantly correlated with injury severity based on the Acute Physiologic and Chronic Health Evaluation (APACHE II) score (r = -0.43 and r = -0.37, respectively). These findings suggest that hepatic oxidative and conjugative metabolism increase significantly over time in patients after acute head injury. An awareness of the potential for pharmacokinetic alterations in similarly metabolized drugs used for patients with severe head injuries is recommended.
Adult↗
Selection process for surgeons in the Asymptomatic Carotid Atherosclerosis Study.
BACKGROUND AND PURPOSE: The Asymptomatic Carotid Atherosclerosis Study is a prospective, multicenter, randomized clinical trial of carotid endarterectomy for the treatment of asymptomatic hemodynamically significant stenosis. This report describes the selection process for participating surgeons in the trial. METHODS: The Surgical Management Committee established guidelines for minimal annual experience and maximum neurological morbidity and mortality for surgeons to qualify to participate in the study. For approval, a surgeon must perform at least 12 carotid endarterectomies per year. Based on a review of the surgeon's last 50 consecutive endarterectomies, the combined neurological morbidity and mortality rate must be no greater than 5% for all indications and no greater than 3% for endarterectomies performed on asymptomatic patients. RESULTS: One hundred sixty-four surgeons from 48 centers applied for approval: 117 were approved, 17 were rejected, and 30 were not reviewed. The 117 approved surgeons submitted a total of 5,641 endarterectomies with a combined mortality and neurological morbidity rate of 2.3% for the variety of indications for operation. CONCLUSIONS: This overall experience with carotid endarterectomy is one of the largest series reported to date. The data from approved surgeons are well within the range of acceptable neurological morbidity and mortality rates recommended by the Stroke Council of the American Heart Association, which attests to the overall quality of the surgeons participating in the study.
Carotid Artery Diseases↗
Identification of capric acid as a potent vasorelaxant of human basilar arteries.
To determine whether naturally occurring fatty acids, especially saturated ones, might act directly as vasodilators, segments of human basilar arteries and umbilical arteries were precontracted submaximally with prostaglandin F2 alpha and then exposed to different saturated fatty acids (C4 through C16) or unsaturated fatty acids (C14:1, C18:1, C18:2, and C18:3) at concentrations from 4 microM to 4 mM. The results showed caprate (C10) to be the most potent vasorelaxant and basilar arteries to be more responsive (EC50 = 63 microM) than umbilical arteries (EC50 = 780 microM). Caprate also inhibited contractions elicited by KCl, serotonin, and the thromboxane analogue U46619. The relaxation was independent of the endothelium, and potency was not related to the weak capacity of caprate to inhibit Ca(2+)-induced contractions of K(+)-depolarized basilar arteries. The pattern of potencies for the arteries differed, but among unsaturated fatty acids the monounsaturated (C14:1, C18:1) were more potent than the polyunsaturated (C18:2, C18:3). Comparing the potencies obtained with the concentrations reported for the free fatty acid content of arteries, brain, and plasma indicates that these lipids could influence vasomotion in health and disease.
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗