Airway obstruction in head and neck surgery.
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Airway Obstruction↗
Biomedical subjects
M Taylor
Publications and source records attributed to M Taylor.
Cutaneous and systemic responses during primary and challenge infestations of sheep with the sheep scab mite, Psoroptes ovis.
Lesional area was estimated and lesional mast cells and eosinophils were counted during primary and challenge infestations of sheep with Psoroptes ovis. In addition, circulating basophils and eosinophils and serum P. ovis-specific immunoglobulin IgE antibody were quantified. Expansion of lesional area was significantly less and serum IgE titres significantly greater in challenge than primary infestations. Lesional mast cell hyperplasia and massive eosinophil infiltration accompanied by raised titres of P. ovis antigen-specific IgE antibody were compatible with an IgE-mediated Type-1 allergic reaction, while detection of lesional basophils was suggestive of cutaneous basophil hypersensitivity. The temporal pattern of lesional mastocytosis and eosinophil infiltration and the role of these cells and serum IgE in the immune response is discussed.
Animals↗
Surgical correction of isolated superficial venous reflux reduces long-term recurrence rate in chronic venous leg ulcers.
OBJECTIVES: surgical correction of isolated superficial venous reflux in ulcerated legs may reduce short term recurrence rates but the longer term benefits are unknown. DESIGN: prospective non-randomised cohort study. METHODS: consecutive patients with chronic leg ulcers were prospectively assessed at a one-stop clinic over a 4-year period from July 1995 to July 1999. All patients with ankle brachial pressure indices (ABPI)50.85 were initially treated with weekly four-layer bandaging. Venous duplex studies in all ulcerated legs assessed venous reflux pattern with surgery being offered to all those with isolated superficial reflux, of whom 56% accepted. Patients were advised to wear class two elastic compression stockings after healing. RESULTS: 766 legs in 669 patients were assessed. Six hundred and thirty-three legs had an ABPI50.85, 236 (39%) demonstrating isolated superficial venous reflux. Surgery was performed on 131 of these legs. Twelve and 24 week healing rates were 50% and 72% for operated legs and 62% and 74% for non-operated legs (p=0.67; Kaplan-Meier life table analysis). Recurrence rates at 1, 2 and 3 years were 14%, 20% and 26% for operated legs and 28%, 30% and 44% for non-operated legs (p=0.03; Kaplan-Meier life table analysis). CONCLUSION: surgical correction of superficial venous reflux in legs with chronic leg ulceration may reduce ulcer recurrence rate at 1, 2 and 3 years.
Adult↗
The importance of tibial alignment: finite element analysis of tibial malalignment.
The influence of the tibial plateau orientation on cancellous bone stress was examined by finite element analysis for a cemented device. The objectives of the study were i) to examine the effect of the plateau-ankle angle on the cancellous bone stress, ii) to analyze the significance of the anteroposterior angles of the tibial component on these stresses, and iii) to compare the finite element predictions with clinical data. In general, positioning the tibial plateau in valgus resulted in lower cancellous bone stresses. These results support previous clinical studies, which suggest that overall alignment in valgus results in lower migration rates and lower incidence of loosening.
Biomechanical Phenomena↗
Relationship of vascular maturation in breast cancer blood vessels to vascular density and metastasis, assessed by expression of a novel basement membrane component, LH39.
Angiogenesis, the formation of new vessels, has been demonstrated to be an indicator of prognosis in breast cancer patients. The extent of differentiation of the tumour vessels may affect access of peripheral white cells and egress or invasion of tumour cells. This has not been assessed in relation to tumour microvessel density or other variables and may be a marker of vascular remodelling. LH39 is a monoclonal antibody recognizing an epitope located at the lamina lucida of mature small veins and capillaries but not in newly formed vessels. To study vascular differentiation in breast tumours, we examined the vascular maturation index (VMI) in 12 normal and 50 breast carcinomas and this was correlated with different clinicopathological variables including angiogenesis. Mature vessels were defined by staining with antibodies to both LH39 and to CD31, using double immunohistochemistry, whereas immature vessels stained only for CD31. VMI was defined as the % fraction of mature vessels (LH39-positive) / total number of vessels (CD31-positive). The VMI was significantly higher in normal (54-68.5%; median 66.5%) than in tumours (0-47%; median 8.8%) (P = 0.0005). There was a significant inverse correlation between the tumour VMI and nodal status (Fisher's exact test, P = 0.01) and between high VMI and low thymidine phosphorylase (TP) expression (Mann-Whitney U-test, P= 0.01). No significant association between VMI and tumour size, oestrogen receptor, epidermal growth factor receptor, grade, angiogenesis, patient age, or E-selectin was seen. There was a significant reduction in relapse-free survival (P = 0.01) with high angiogenesis. These findings show that the VMI gives new information on the mechanism of tumour angiogenesis independently from microvessel quantitation, there is a wide variation in the differentiation of tumour vasculature but the degree of capillary differentiation is not associated with quantitative angiogenesis. The VMI identifies a subset of patients who have a high chance of regional node involvement.
Adult↗
Induction of thymidine phosphorylase as a pharmacodynamic end-point in patients with advanced carcinoma treated with 5-fluorouracil, folinic acid and interferon alpha.
Thymidine phosphorylase (TP) is an essential enzyme for the biochemical activation of 5-fluorouracil (5-FU). Interferon upregulates TP in vivo, although the dose and schedule of interferon for optimal biomodulation of 5-FU is not known. In this study, TP activity was measured in peripheral blood lymphocytes (PBLs) from patients with advanced carcinoma receiving treatment with 5-FU and folinic acid. Cohorts of patients were treated with interferon alpha (IFNalpha), immediately prior to 5-FU/folinic acid, at doses of 3 MIU m(-2), 9 MIU m(-2) and 18 MIUm(-2). IFNalpha was administered on day 0 cycle two, day-1 and day 0 cycle three and day-2, day-1 and day 0 cycle four. A fourth cohort was treated with IFNalpha 9 MIU m(-2) three times per week from cycle 2 onwards. Twenty-one patients were entered into the study with 19 evaluable for response. Six patients (32%) had stable disease and 13 (68%) progressive disease. There were no grade-IV toxicities. TP activity was detected in PBLs from all patients with wide interpatient variability in constitutive TP activity prior to chemotherapy, and in response to IFNalpha. 5-FU/folinic acid alone did not induce TP activity but a single dose of IFNalpha led to upregulation of TP within 2 h of administration with a further increase by 24 h (signed rank test, P = 0.006). TP activity remained elevated for at least 13 days (signed rank test, P= 0.02). There were no significant differences in TP activity between schedules or with additional doses of IFNalpha. A single dose of IFNalpha as low as 3 MIU m(-2) can cause sustained elevation of PBL TP activity in vivo indicating that biochemical markers are important pharmacodynamic endpoints for developing optimal schedules of IFNalpha for biomodulation of 5-FU.
Aged↗
In vivo evaluation of a morpholino antisense oligomer directed against tumor necrosis factor-alpha.
Morpholino antisense oligomers directed against the cytokine tumor necrosis factor (TNF-alpha) can specifically inhibit production of TNF-alpha by macrophages in vitro. To evaluate the efficacy of morpholino antisense in vivo, we characterized a mouse model of increased pulmonary TNF-alpha production and inflammation in response to aerosolized endotoxin. Pretreatment of mice by intranasal (i.n.) insufflation of oligomers (30 microl of 100 microM/ml) 12 hours prior to lipopolysaccharide (LPS) exposure resulted in specific and consistent inhibition of TNF-alpha production by the oligomer MAS-2, whereas no effect was observed with a sequence-scrambled control (% inhibition 31.5 +/- 3.5 vs. 1.3 +/- 8.0, respectively, p < 0.005). Dose-response analysis showed similar efficacy for MAS-2 at 25-100 microM/ml and diminished effects with lower concentrations. Inhibition of TNF-alpha did not alter the increase in neutrophils seen in bronchoalveolar lavage (BAL) fluid, a result consistent with observations using i.n. administration of neutralizing anti-TNF-alpha antibody or TNF receptor knockout mice. The results establish that morpholino oligomers directed against cytokine targets can function in vivo. Additional studies of other targets and administration protocols to improve efficacy are warranted.
Administration, Intranasal↗
Standard dose (Mayo regimen) 5-fluorouracil and low dose folinic acid: prohibitive toxicity?
Despite the perception that standard 5-fluorouracil/folinic acid (5-FU/FA) (425 mg/m2 per day and 20 mg/m2 per day intravenously once daily x 5 every 4 or 5 weeks) is well tolerated, we have been impressed by toxicity seen and frequent need for dose modification. We performed a retrospective analysis to quantitate the proportion of patients experiencing toxicity and attempted to identify associated clinical characteristics. One hundred thirty-four patients received 5-FU/FA at standard doses described by the Mayo regimen. Patient characteristics were as follows: female 35%, median age 66 years, Eastern Cooperative Oncology Group performance status less than or equal to 2, 96%. Sixty-eight percent received chemotherapy for metastatic disease. Forty-seven patients (35%+/-8%) experienced significant toxicity and were unable to receive the second cycle as scheduled: 76% required dose reduction, 11% discontinued therapy (including two toxic deaths), 11% discontinued therapy during the first cycle, and 2% required dose delay. Logistic regression was used to explore the following as predictors of toxicity: age, sex, performance status, adjuvant versus metastatic setting, prior chemotherapy, prior radiation, mean corpuscular volume, red blood cell distribution width, albumin, alkaline phosphatase, aspartate aminotransferase, bilirubin, and calculated creatinine clearance. No clinical characteristic was found to predict toxicity. Only high bilirubin approached statistical significance. We conclude that standard 5-FU/FA, when used in the general population, is associated with significant toxicity. Known clinical characteristics are not helpful in predicting toxicity. The lack of previous formal phase I evaluation of this regimen of 5-FU/FA raises concerns regarding its safety and generalizability in clinical practice.
Adult↗
Induced hypothermia during emergency department thoracotomy: an animal model.
BACKGROUND: Induced hypothermia is used clinically to prevent ischemic injury during elective procedures. We present an animal model of asanguinous hypothermic (10 degrees C) circulatory arrest, induced through a left anterior lateral thoracotomy after exsanguinating uncontrolled hemorrhage. METHODS: Through a left anterior thoracotomy, 26 swine (45-70 kg) sustained a laceration of the descending thoracic aorta, producing exsanguinating uncontrolled hemorrhage. After 5 minutes of severe hypotension (systolic BP <20 mm Hg), a 22 French Foley catheter was directed cephalad through the enlarged aortic wound. A solution (containing 42.5 mmol/L K+ and precooled to 1 degrees C) was infused to arrest/preserve the heart and brain. A second 24 French Foley catheter was then directed caudally through the same wound. The right atrium was opened to drain the venous system. The animal was cooled with a cardiopulmonary bypass pump (>5L/min) through the Foley catheters. Once 10 degree C was reached, a cannula was placed to the aortic root and the aortic laceration repaired. The animal was maintained at 10 degree C for a total of 90 minutes. Before the rewarming process, the circulation was rinsed with a solution containing normal levels of electrolytes followed by infusion of whole blood. Rewarming was performed by maintaining a 10-degree gradient on the heat exchanger. The first 16 animals were used in nonsurvival experiments to develop the technique and to record dural temperatures and electroencephalogram tracings. The last 10 animals were used to determine long-term survival and neurologic outcome. Group I: seven animals were kept at < 10 degrees C with flows less than 2L/min. Group II: three animals underwent 20, 30, and 40 minutes of no flow once they were cooled to 10 degrees C. After 6 weeks of survival and neurologic examinations, the brains were fixed for histologic evaluations. RESULTS: The average time to cool the head to 18 degrees C and 10 degrees C was 6 minutes and 12 minutes, respectively. The hematocrit fell below 2% by the end of the cooling period. A total of 7 of the 10 animals from the long-term study survived. Group I: five of seven animals survived. Four of the survivors had no appreciable neurologic deficits, were fully functional at 6 weeks, and had no evidence of histologic injury. One of the five survivors in this group had moderate neurologic disability. Of the two animals that died, one died from air embolism from the i.v. line. The second death was in an animal for which maximal cooling to 2.7 degrees C was attempted. Group II: The first two animals that had "no flow" for 20 and 30 minutes were fully functional and had normal neurologic examinations. However, the second animal was found to have brain injury on histologic examination. The last animal in this group died of accidental extubation during recovery. CONCLUSION: Induction of hypothermic arrest through the chest after exsanguination is possible. The further development of this technique may provide an extended state of "suspended animation" to allow for repairs of hemorrhaging injuries in trauma patients who require emergency department thoracotomy.
Animals↗
Molecular biology and neurosurgery in the third millennium.
The application of techniques in molecular biology to human neurosurgical conditions has led to an increased understanding of disease processes that affect the brain and to novel forms of therapy that favorably modify the natural history of many of these conditions. Molecular strategies are currently being either used or sought for brain tumors, stroke, neurodegenerative diseases, vascular malformations, spinal degenerative diseases, and congenital malformations of the central nervous system. Considering that the structure of deoxyribonucleic acid was ascertained by Watson and Crick as recently as 1953, the progress that has been made to implement molecular medicine in clinical practice has been meteoric. More than 2000 patients have been treated in approved gene therapy trials throughout the world. Many of these patients have been treated for neurological diseases for which conventional medical therapies have been of limited utility. As part of this continuing series on advances in neurosurgery in the third millennium, we first reflect on the history of the nascent field of molecular biology. We then describe the powerful techniques that have evolved from knowledge in this field and have been used in many publications in Neurosurgery, particularly within the past decade. These methods include commonly used techniques such as advanced cytogenetics, differential display, microarray technology, molecular cell imaging, yeast two-hybrid assays, gene therapy, and stem cell utilization. We conclude with a description of the rapidly growing field of bioinformatics. Because the Human Genome Project will be completed within 5 years, providing a virtual blueprint of the human race, the next frontier (and perhaps our greatest challenge) will involve the development of the field of "proteomics," in which protein structure and function are determined from the deoxyribonucleic acid blueprint. It is our conviction that neurosurgeons will continue to be at the forefront of the treatment of patients with neurological diseases using molecular strategies, by performing essential research leading to increased understanding of diseases, by conducting carefully controlled studies to test the effects of treatments on disease processes, and by directly administering (by neurosurgical, endovascular, endoscopic, or stereotactic means) the treatments to patients.
Cytogenetics↗
Neural correlates of theory-of-mind reasoning: an event-related potential study.
Everyday understanding of human behavior rests on having a theory of mind--the ability to relate people's actions to underlying mental states such as beliefs and desires. It has been suggested that an impaired theory of mind may lie at the heart of psychological disorders that are characterized by deficits in social understanding, such as autism. In this study, we employed the event-related potential methodology to index the activity of neural systems that are engaged during theory-of-mind reasoning in adults. Specifically, neural activity elicited by tasks that required thinking about mental as compared with nonmental representations (i.e., beliefs vs. photographs) was characterized by a focally enhanced positivity over left frontal areas, which was diminished over left parietal areas. These findings provide an important perspective on both children's theory-of-mind development and the neurobiology of disorders in which theory of mind seems to be impaired.
Adolescent↗
Referral patterns for gynaecological radiotherapy in Victoria.
A retrospective chart review was undertaken on all patients in Victoria who were referred for radiotherapy for a gynaecological cancer from February 1997 to January, 1998. Three hundred and ten patients were identified which represents less than one-third of all gynaecological cancers diagnosed in Victoria each year. Ninety-two of the 310 patients (30%) referred for radiotherapy were managed without the prior involvement of a certified gynaecological oncologist. The 310 patients included 95 patients with cervical cancer, 33 patients with ovarian cancer and 142 patients with endometrial cancer. The initial management strategies employed for patients with the major gynaecological cancers varied depending on the source of referral. This difference was most marked in endometrial cancer due mainly to differing indications for full surgical staging and subsequent referral for radiotherapy both between types of specialists and also between gynaecological oncology units. The development of evidence based guidelines in the major gynaecological cancers should lead to a more uniform approach to the care of women with gynaecological malignancies.
Delivery of Health Care↗
Modulation of the acute phase response by altered expression of the IL-1 type 1 receptor or IL-1ra.
A complete understanding of the role for endogenously produced interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-alpha), and IL-1 receptor antagonist (IL-1ra) in the acute phase response to inflammation remains unknown. In the present studies, knockout mice lacking either a functional IL-1 type I receptor (IL-1RI(-/-)), a TNF type I receptor (TNFR-I(-/-)), or both IL-1 type I and TNF type I receptors (IL-1RI(-/-)/TNFR-I(-/-)) received a turpentine abscess. Additional mice deficient in IL-1ra protein (IL-1ra(-/-)) or overexpressing IL-1ra protein (IL-1ra(tg)) were similarly treated. After a turpentine abscess, IL-1 receptor knockout mice exhibited an attenuated inflammatory response compared with wild-type or animals lacking a functional TNFR-I. Mice overexpressing IL-1ra also had an attenuated hepatic acute phase protein response, whereas IL-1ra knockout mice had a significantly greater hepatic acute phase response. We conclude that the inflammatory response to a turpentine abscess is the result of a balance between IL-1ra expression and IL-1 binding to its type I receptor. Endogenously produced IL-1ra plays a central role in mitigating the magnitude of the IL-1-mediated inflammatory response and, ultimately, the outcome to a turpentine abscess.
Abscess↗
Comparison of the effect on bronchial hyperresponsiveness of beclomethasone dipropionate administered via a novel multidose dry-powder inhaler or a conventional pressurised metered dose inhaler.
BACKGROUND: Treatment with inhaled corticosteroids improves symptoms and reduces bronchial hyperresponsiveness (BHR) associated with asthma. Delivery of drugs into the lung is dependent on the inhaler device. Furthermore, environmental concerns regarding the use of chlorofluorocarbon propellants in pressurised inhalers and patient acceptability of inhaler devices both influence the extent of use of different delivery systems. OBJECTIVES: To compare the efficacy of beclomethasone dipropionate (BDP) administered via a novel multidose dry-powder inhaler (DPI) and a conventional pressurised metered-dose inhaler (pMDI) with spacer in patients with BHR. METHODS: A randomised, double-blind, crossover study was carried out in a group of 27 patients (aged 19-55 years) with a clinical diagnosis of reversible airway disease, who demonstrated BHR to methacholine (PD(20) < or =6.4 mg). Each patient received BDP (< or =2 mg/day) via the DPI or pMDI, for periods of 4 weeks. The randomised treatment periods were preceded by 3-week washout periods when no corticosteroid was used. Five clinic visits marked the start and end of each study phase. The primary efficacy endpoint was BHR as defined by the pharmacodynamic parameter, PD(20), which was determined at the start and end of each treatment period. Clinical endpoints including lung function, symptoms and adverse events were also evaluated. RESULTS: Both treatments caused a significant decrease in BHR (p<0.05 vs. pre-treatment values). Mean +/- SD changes in log PD(20) were: DPI 0.59+/-1.29; pMDI 0.59+/-0.94 mg. There was no statistically significant difference between treatments and no evidence of a carry-over effect between treatments on BHR. Clinical efficacy and safety parameters also demonstrated no statistically significant treatment differences, and patients found the DPI easier to use. CONCLUSION: Efficacy of BDP in reducing BHR is comparable via the DPI and pMDI plus spacer.
Administration, Inhalation↗
Pancreaticoduodenectomy after downstaging of pancreatic carcinoma by chemotherapy.
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Adenocarcinoma↗
The pathology of spontaneous paratuberculosis in the North American bison (Bison bison).
Gross and histopathologic examinations were performed on 70 North American bison (Bison bison) from a Mycobacterium avium paratuberculosis culture-positive herd. The bison examined were part of a breeding herd totaling 2,800 animals. Eight of 70 (11%) animals had gross findings of intestinal mucosal thickening, and 16 of 70 (23%) of the animals had enlarged mesenteric lymph nodes. Histologic lesions compatible with Johne's disease were diagnosed in 30 of 70 (43%) bison on the basis of the demonstration of noncaseating granulomatous inflammatory infiltrates and of one or more acid-fast bacilli characteristic of Mycobacterium avium paratuberculosis. A suspicious diagnosis of Johne's disease was obtained in 11 of 70 (16%) bison on the basis of the observation of noncaseating granulomatous inflammatory infiltrates without demonstrable acid-fast bacteria. Twenty-nine of 70 (41%) animals were assessed as histologically paratuberculosis free. Histologic results were compared to Johne's disease tests such as culture, serology, and polymerase chain reaction, which were performed on some of the cohort animals.
Animals↗
Hemodynamic effects of epoprostenol in patients with systemic sclerosis and pulmonary hypertension.
STUDY OBJECTIVES: To determine the cause of pulmonary hypertension (PH) in systemic sclerosis (SSc) patients since PH can occur because of pulmonary arteriopathy, pulmonary parenchymal destruction, and left ventricular cardiac dysfunction. DESIGN AND SETTING: Consecutive case series in a university hospital. PATIENTS: Nine SSc patients with PH (mean pulmonary artery pressure, 41 mm Hg), with (n = 6) or without (n = 3) concomitant interstitial lung disease (ILD). METHODS: Acute infusion of epoprostenol was begun at 2 ng/kg/min and was titrated upward at a rate of 2 ng/kg/min every 30 min until symptomatic complications developed or pulmonary artery vascular resistance (PVR) was reduced by 50%. RESULTS: Eight of nine patients demonstrated a reduction of > or = 20% in PVR, suggesting that vasoreactivity is common despite the presence of significant ILD. A single patient had no response to infusion with unchanged hemodynamics and oxygenation. One patient developed hypoxemia as cardiac output increased, suggesting a worsening of ventilation/perfusion matching or the presence of an anatomic shunt. Acute pulmonary edema developed in one patient at an infusion rate of 6 ng/kg/min. The results of cardiac catheterization suggested that pulmonary edema was caused by SSc heart disease. CONCLUSION: SSc patients with ILD have diverse and sometimes multiple causes of PH that can be determined by short-term epoprostenol infusion. Beneficial effects can be obtained from epoprostenol despite extensive ILD.
Adult↗
Performance of black and white South African children on the Wechsler Intelligence Scale for Children--Revised and the Kaufman Assessment Battery.
The validity of traditional intelligence tests for cultural groups that differ from those for whom the tests were normed has come under scrutiny. This is particularly the case for the previously disadvantaged black majority in South Africa. The Kaufman Assessment Battery for Children (K-ABC) is reportedly a relatively nondiscriminatory test of intellectual functioning. This study compared the performance of 21 black and 35 white third-grade South African children on the K-ABC and the Wechsler Intelligence Scale--Revised (WISC-R) at two schools for children with learning problems. While the WISC-R Verbal and Full Scale IQ of black children were significantly lower than that of whites, there was no significant difference between these groups on the K-ABC. Teachers' ratings for white and black pupils were acceptably concordant with students' performance on the K-ABC but not on the WISC-R. Support is provided for the usefulness of the K-ABC as a relatively nondiscriminatory alternative to the WISC-R for South African children.
Black or African American↗