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Biomedical subjects

J A McGuigan

Publications and source records attributed to J A McGuigan.

At least 19 recordsLinked to original sources

Descending necrotising mediastinitis: a safe treatment algorithm.

Descending necrotising mediastinitis can complicate oropharyngeal infection and has a high associated mortality. We present three cases treated in our department and propose a treatment algorithm based on our experience and literature review. The primary oropharyngeal infection was peritonsillar abscess in two cases and odontogenic abscess in one. Two patients underwent cervicotomy and later thoracotomy. The third underwent cervicotomy with transcervical mediastinal drainage and later required pericardial drainage via a subxiphoid incision. All recovered fully and were discharged within 6 weeks. To enable successful treatment, diagnosis needs to be prompt and surgical drainage adequate. Thoracic management of the chest is essential.

Adolescent↗

Mediastinitis: a life-threatening complication of acute tonsillitis.

Acute tonsillitis is a common condition and usually runs a benign course. However life-threatening complications do still occur, even in this postantibiotic era. Infection can spread downwards into the mediastinum through the anatomic cervical spaces, causing widespread cellulitis, necrosis, abscess formation and sepsis. We present a case of descending mediastinitis in an 18-year-old woman, arising from her first episode of tonsillitis and treated successfully by surgical drainage. We believe that an awareness of this complication, early diagnosis using computed tomography scanning, and prompt, adequate surgical drainage will reduce morbidity and mortality.

Acute Disease↗

Treatment and outcomes of oesophageal perforation in a tertiary referral centre.

OBJECTIVE: The diagnosis and management of oesophageal perforation continues to challenge clinicians. We present our experience of perforated oesophagus in a Tertiary Referral Centre for Thoracic and Oesophageal Surgery. METHODS: Between 1985 and 2000, 75 patients (40 male) with oesophageal perforation were treated in out unit; age range 24-89, median 63. Retrospective review of these cases has been performed. RESULTS: There were 12 deaths (16%). With increases in time from perforation to diagnosis, there was a stepwise increase in the mortality rate. Immediate diagnosis 5%; early diagnosis (1-24h) 14%; late diagnosis (>24h) 44% (P>or=0.002). Site of perforation, aetiology, and treatment strategy had no influence on mortality. The only independent predictor of mortality identified was time to diagnosis from perforation (beta 0.429, P=0.001). Time to definitive management in those undergoing an operative procedure had no influence on outcome with multivariate analysis. CONCLUSIONS: Prompt recognition of the diagnosis of oesophageal perforation and rapid institution of supportive measures, followed by an appropriate, patient specific treatment option optimises the chance of a successful outcome. The wide range of presentation of oesophageal perforation necessitates individualisation of treatment.

Adult↗

Increased nm23 immunoreactivity is associated with selective inhibition of systemic tumour cell dissemination.

AIMS: In vitro transfection experiments show that the nm23 gene suppresses metastasis, although the evidence from clinical studies is contradictory. The purpose of this study was to investigate whether nm23 selectively influences systemic, pleural, and lymphatic metastasis in non-small cell lung cancer (NSCLC). METHODS: Forty two patients undergoing resection of NSCLC and lymph node sampling were enrolled prospectively. In each case, a bone marrow aspirate, pleural lavage, and lymph nodes were assessed using immunohistochemistry for epithelial antigens and morphology. The intensity of nm23-H1 immunoreactivity of the primary tumour was compared with the internal control of normal bronchial epithelium in 32 cases where available. The microvessel count (MVC) of each tumour was determined using immunohistochemistry for the endothelial cell marker CD34. RESULTS: Tumour cell dissemination was detected in the bone marrow in 18 patients, in the pleura in seven, and in the lymph nodes in 21. Increased immunoreactivity for nm23 was found in the primary tumour in six patients, with none having tumour cells in the bone marrow, compared with 12 of 26 patients who showed nm23 immunoreactivity equal to or less than the control (Fisher's exact test: p = 0.043). This effect was confirmed to be independent of the MVC on multivariate analysis. There was no significant difference in the incidence of pleural or lymphatic tumour cell dissemination between the two groups. CONCLUSION: nm23 appears to be a suppressor of systemic, but not lymphatic, metastasis in primary NSCLC.

Aged↗

Microsatellite analysis provides evidence of neoplastic transformation in long-segment, but not in short-segment, Barrett's oesophagus.

It has been suggested that the high prevalence of short segments of specialised intestinal metaplasia (SIM) at the gastro-oesophageal junction is associated with the rising incidence of oesophageal adenocarcinoma. Our aims were to document the prevalence of short segments of SIM at the gastro-oesophageal junction in patients attending for routine endoscopy and to determine if there was molecular evidence of neoplastic transformation in those with SIM. Patients (n = 101) were recruited from randomly selected upper gastro-intestinal endoscopy lists. Biopsy specimens were taken at the squamo-columnar junction to assess the prevalence of SIM. Frozen sections were assessed for molecular evidence of neoplastic transformation using microsatellite analysis. Squamo-columnar biopsies were suitable for analysis in 95 patients, of whom 20 (21%) had oesophagitis and 2 (2%) had Barrett's oesophagus (>3 cm of endoscopically apparent columnar-lined oesophagus). Twenty patients had SIM at the gastro-oesophageal junction, including 2 with Barrett's oesophagus and 18 with short segments of SIM, one of whom had an associated intramucosal adenocarcinoma detected incidentally by histology. Three of the 20 cases with SIM exhibited novel microsatellite alleles, 2 with Barrett's oesophagus and 1 with short segment SIM and an associated adenocarcinoma. The 18 patients with short segments of SIM at the gastro-oesophageal junction were significantly older than those without SIM.

Adenocarcinoma↗

Muscle sparing thoracotomy: a biomechanical analysis confirms preservation of muscle strength but no improvement in wound discomfort.

OBJECTIVES: This study compares the posterior auscultatory triangle thoracotomy incision (muscle sparing) with full posterolateral thoracotomy (where latissimus dorsi muscle is always cut across its full width), with particular attention to the difference between latissimus dorsi muscle strength, post operative pain and chronic wound related symptoms. METHODS: Ten patients who had undergone auscultatory triangle thoracotomy (ATT) at least 1 year previously were matched with ten patients who had undergone posterolateral thoracotomy (PLT). Each pair was matched for age, sex, dominant hand, side of the operation, time since operation and presence or absence of history of previous muscle training. Latissimus dorsi muscle strength was assessed by testing the shoulder adduction strength through an arc of 90-0 degrees using isokinetic technique. Early post-operative pain was assessed indirectly by calculating the analgesic requirement in the first 5 post-operative days. A subjective assessment of chronic post-thoracotomy pain was made using a questionnaire presented to the patients at the time of muscle testing. Variability of the torque curves, recorded as coefficient of variance at the time of muscle strength testing, provided objective measurements of chronic pain. Data were analysed using two sample t-tests. RESULTS: All patients reported at least one chronic post-thoracotomy symptom. There was no significant difference between the two groups in terms of acute or chronic wound pain and other long term wound related symptoms. Shoulder adduction strength was 24% greater in ATT than PLT (95% confidence limits=1-43%, P=0.04). CONCLUSIONS: All thoracotomy patients have long term wound related symptoms. This situation is not improved by performing a muscle sparing incision. However thoracotomy through the triangle of auscultation can preserve latissimus dorsi strength which is compromised in a posterolateral thoracotomy incision. We therefore recommend that a muscle sparing thoracotomy be considered for patients where preservation of muscle strength is deemed important, providing the operation is not compromised due to inadequate access.

Adolescent↗

Effect of thoracotomy and lung resection on exercise capacity in patients with lung cancer.

BACKGROUND: Resection is the treatment of choice for lung cancer, but may cause impaired cardiopulmonary function with an adverse effect on quality of life. Few studies have considered the effects of thoracotomy alone on lung function, and whether the operation itself can impair subsequent exercise capacity. METHODS: Patients being considered for lung resection (n = 106) underwent full static and dynamic pulmonary function testing which was repeated 3-6 months after surgery (n = 53). RESULTS: Thoracotomy alone (n = 13) produced a reduction in forced expiratory volume in one second (FEV1; mean (SE) 2.10 (0.16) versus 1.87 (0.15) l; p<0.05). Wedge resection (n = 13) produced a non-significant reduction in total lung capacity (TLC) only. Lobectomy (n = 14) reduced forced vital capacity (FVC), TLC, and carbon monoxide transfer factor but exercise capacity was unchanged. Only pneumonectomy (n = 13) reduced exercise capacity by 28% (PVO2 23.9 (1.5) versus 17.2 (1.7) ml/min/kg; difference (95% CI) 6.72 (3.15 to 10.28); p<0.01) and three patients changed from a cardiac limitation to exercise before pneumonectomy to pulmonary limitation afterwards. CONCLUSIONS: Neither thoracotomy alone nor limited lung resection has a significant effect on exercise capacity. Only pneumonectomy is associated with impaired exercise performance, and then perhaps not as much as might be expected.

Exercise Test↗

Simultaneous cardiac surgery with pulmonary resection: presentation of series and review of literature.

BACKGROUND: The issue of performing simultaneous pulmonary resection and cardiac surgery in patients with coexisting lung carcinoma and ischaemic heart disease remains controversial. We report our experience and review the literature. METHODS: Thirteen patients (male ten, female three; mean age 65 years) underwent simultaneous cardiac surgery and pulmonary resection. Lung pathology consisted of primary lung carcinoma (n = 10), benign disease (n = 2) and carcinoid (n = 1). Lung resections included pneumonectomy (n = 3), lobectomy (n = 4), segmentectomy (n = 1) and local excision (n = 5). Cardiac procedures consisted of coronary artery bypass grafting (CABG) in 11, aortic valve replacement in one and mitral valve repair with CABG in one patient. In all but one case the lung resection was performed prior to heparinization and cardiopulmonary bypass (CPB). In two patients, with suitable coronary anatomy, myocardial revascularization without CPB was performed to reduce morbidity. RESULTS: There was no hospital mortality. Postoperative blood loss and ventilation requirements were reduced in the patients who were operated on without CPB. Prolonged ventilatory support was required in two cases. All patients with benign pathology are alive. In the lung cancer group there have been five late deaths: disseminated metastatic disease (n = 3), anticoagulant related haemorrhage (n = 1) and broncho-pleural fistula (n = 1). Of the remaining five patients four are alive and disease free 7-23 months post-operatively; one patient has recurrent disease 40 months post-operatively. CONCLUSIONS: Simultaneous pulmonary resection and cardiac surgery is associated with acceptable operative morbidity and mortality. In patients with lung carcinoma long-term survival was determined by tumour stage. The avoidance of CPB may be advantageous by decreasing blood loss and ventilation requirements.

Aged↗

Comparison of p53 and DNA content abnormalities in adenocarcinoma of the oesophagus and gastric cardia.

This study examined the association between 17p allelic loss, p53 gene mutation, p53 protein expression and DNA aneuploidy in a series of adenocarcinomas arising in the oesophagus and gastric cardia. 17p allelic loss was detected in 79% (15 of 19) of oesophageal and in 83% (29 of 35) of gastric adenocarcinomas. p53 mutations were detected in 70% (14 of 20) and 63% (26 of 41) of oesophageal and of gastric adenocarcinomas respectively. Both tumour types were associated with a predominance of base transitions at CpG dinucleotides. In five cases of oesophageal adenocarcinoma, the same mutation was detected both in tumour and in adjacent dysplastic Barrett's epithelium. Diffuse p53 protein expression was detected in 65% (13 of 20) and 59% (24 of 41) of oesophageal and of gastric tumours, respectively, and was associated with the presence of p53 missense mutation (Chi-squared, P < 0.0001). DNA aneuploidy was detected in 80% (16 of 20) of oesophageal and in 70% (28 of 40) of gastric tumours. No association was found between p53 or DNA content abnormalities and tumour stage or histological subtype. In conclusion, this study detected a similar pattern of p53 alterations in adenocarcinoma of the oesophagus and gastric cardia--molecular data consistent with the observation that these tumours demonstrate similar clinical and epidemiological features.

Adenocarcinoma↗

Barrett's oesophagus: microsatellite analysis provides evidence to support the proposed metaplasia-dysplasia-carcinoma sequence.

The development of adenocarcinoma in Barrett's oesophagus is proposed to occur via a stepwise progression recognised histologically as a metaplasia-dysplasia-carcinoma sequence. In order to identify chromosomal loci involved in the malignant transformation of Barrett's epithelium and the development of oesophageal adenocarcinoma, microsatellite analysis was carried out on 17 cases of Barrett's-associated oesophageal adenocarcinoma. Samples of premalignant Barrett's epithelium adjacent to adenocarcinoma were obtained from seven of these cases. Allelic imbalance was detected in > 45% of informative cases of oesophageal adenocarcinoma on chromosome arms 3q (65%), 4q (71%), 5q (59%), 6q (59%), 9p (50%), 9q (47%), 12p (47%), 12q (65%), 17p (76%), and 18q (75%). Allelic imbalance at 4q, 17p, and 18q was significantly higher than the upper 95% confidence interval for background allelic imbalance. Allelic imbalance was detected at several loci in the premalignant epithelium from five of the seven cases studied. These loci included several chromosomal arms that had demonstrated high levels of allelic imbalance in oesophageal adenocarcinoma, namely, 4q (one case), 5q (two cases), 9 (three cases), 12q (five cases), 17p (four cases), and 18q (two cases). Novel microsatellite alleles were detected in both premalignant and malignant Barrett's epithelium. In three cases, dysplastic Barrett's epithelium and adjacent adenocarcinoma demonstrated the same pattern of novel microsatellite alleles at a number of loci. In conclusion, these data indicate chromosomal loci which may be specifically involved in the histological progression of Barrett's epithelium. The detection of shared novel microsatellite alleles in premalignant and malignant Barrett's epithelium is consistent with a process of clonal expansion underlying this progression.

Adenocarcinoma↗

Apparent Mg2+-adenosine 5-triphosphate dissociation constant measured with Mg2+ macroelectrodes under conditions pertinent to 31P NMR ionized magnesium determinations.

Using Mg2+ macroelectrodes based on the sensor ETH 7025 and accurate Mg2+-EDTA buffer solutions, the apparent Mg2+-ATP dissociation constant (Kapp) was measured at 25 and 37 degrees C in background solutions mimicking the cationic intracellular milieu of muscle cells. The mean +/- SD (in microM) at 25 degrees C was 157.0 +/- 13 (n = 4), 127.5 +/- 12.0 (n = 11), 101.0 +/- 9.0 (n = 4) and at 37 degrees C was 106.6 +/- 9.6 (n = 4), 87.4 +/- 4.9 (n = 4), 78.1 +/- 2.0 (n = 4) at pH values of 6.7, 7.2, and 7.7, respectively. The dependence of Kapp at 25 degrees C on the ionic strength was also measured, the mean +/- SD (microM) being 61.9 +/- 2.2 (n = 3), 127.5 +/- 12 (n = 11), and 243.0 +/- 11.8 (n = 3) at ionic strengths of 0. 087, 0.156 (normal background), and 0.3 m, respectively. These values are larger than the Kapp values most commonly used in the literature (87.4 microM compared to 38 microM at pH 7.2 and 37 degrees C) to estimate the [Mg2+]i in 31P NMR experiments, attributed to the difficulties in setting the [Mg2+]i without the use of Mg2+ buffer solutions. If these new values are used, the literature values for [Mg2+]i estimated by 31P NMR increase by a factor of around 1.5, making them similar to values obtained by direct Mg2+ microelectrode measurements.

Adenosine Triphosphate↗

Total thoracic esophagectomy for esophageal cancer.

BACKGROUND: Many current methods of esophageal resection have drawbacks that result in inadequate proximal resection, inadequate lymphadenectomy, and difficult gastric and splenic access. We describe a technique that allows reliable and safe access to the chest, abdomen, and neck. STUDY DESIGN: From 1988 to 1995, 113 patients (82 men; mean age 65.3 +/- 4.5 years) with carcinoma of the esophagus or esophagogastric junction (middle third in 34, lower third in 41, and cardia in 38) underwent total thoracic esophagectomy. The histology was adenocarcinoma in 71 (62.8%), squamous cell carcinoma in 32 (28.3%), and undifferentiated carcinoma in 10 (8.9%) of the patients; 57 tumors (50.5%) were stage III. The esophagus and stomach were mobilized through a left thoracoabdominal incision. After completion of the esophageal resection, the fundus of the stomach was sutured to the esophageal stump to allow later delivery of the stomach into the neck. The esophagogastric anastomosis was performed with continuous single-layer absorbable suture through a left oblique cervical incision. RESULTS: The mean duration of the operation was 309.2 +/- 47.9 minutes. Hospital stay ranged from 5 to 49 days (median, 12 days). The perioperative mortality rate was 4.4%. Anastomotic leak occurred in six patients (5.3%), one of whom died. The proximal resection margin was microscopically free of tumor in all cases, and with a minimum followup period of 18 months, there has been no anastomotic recurrence in any patient. Actuarial survival at 1 year was 63.4% +/- 4.9%, at 3 years 41.4% +/- 5.9%, and at 5 years 22.7% +/- 6.3%. CONCLUSIONS: Total thoracic esophagectomy through the left chest with a separate left cervical incision allows clear access to the esophagus and stomach and good tumor clearance. This procedure may be performed with a low rate of anastomotic leakage, a very low mortality rate, and no anastomotic tumor recurrence.

Adenocarcinoma↗

Allelotype analysis of adenocarcinoma of the gastric cardia.

To identify chromosomal loci involved in the development of proximal gastric adenocarcinoma, this study delineated the pattern of allelic imbalance in a series of 38 adenocarcinomas arising in the gastric cardia. A total of 137 microsatellite markers covering all autosomal arms, excluding acrocentric arms, were analysed. A mean of 35 out of a total of 39 chromosomal arms studied were informative for each patient. The tumour group demonstrated a high level of allelic imbalance, with an observed median fractional allelic imbalance of 0.47 for the 29 intestinal-type adenocarcinomas and 0.54 for the nine diffuse-type adenocarcinomas. Allelic imbalance was detected in >50% of informative cases in both histological subtypes on a number of chromosomal arms. In the intestinal subtype, these included, 3p (61%), 4q (71%), 5q (59%), 8p (60%), 9p (65%), 9q (83%), 12q (52%), 13q (52%), 17p (78%) and 18q (70%). A higher incidence of allelic imbalance was detected on chromosome 16q in tumours of the diffuse type relative to those of the intestinal type. A more detailed mapping on chromosomes 4q and 6q identified a number of cases with subchromosomal breakpoints. In conclusion, this analysis has indicated regions of the genome potentially involved in the development of proximal gastric carcinomas.

Adenocarcinoma↗

Calibration of Mg(2+)-selective macroelectrodes down to 1 mumol l-1 in intracellular and Ca(2+)-containing extracellular solutions.

Using Mg(2+)-selective macroelectrodes based on the neutral carriers ETH 7025 and ETH 5506, methods were developed to determine accurately the apparent binding constant (Kapp) and purity, and hence the ionized magnesium concentration ([Mg2+]), in Ca(2+)-free, Mg2+ buffer solutions manufactured with either CDTA (trans-1,2-diaminocyclohexane-N,N,N',N'-tetraacetic acid monohydrate) or EDTA. In nominally Ca(2+)-free solutions, calibration of the macroelectrodes was possible down to 1 mumol l-1 in both intracellular (ETH 7025)- and extracellular (ETH 5506)-like physiological solutions. The measured [Mg2+] in the buffer solutions overlapped with the [Mg2+] set by dilution alone, suggesting that the method was reliable. These buffer solutions could then be used to manufacture standard Mg2+ solution containing known [Mg2+] at a set calcium concentration. Ca2+ sensitivity limits the use of ETH 7025 and, for extracellular measurements in Ca(2+)-containing solutions, Mg(2+)-selective macroelectrodes manufactured with ETH 5506 were the electrodes of choice. In 0.5-0.9 mmol l-1 Ca+, measurement of [Mg2+] was possible down to 10 mumol l-1. At [Mg2+] greater than 0.25 mmol l-1 there was no interference from Ca2+ (0.5-1.5 mmol l-1). With CDTA and/or EDTA buffer solutions there was a wide variation between the calculated values for the [Mg2+] and the measured [Mg2+] (the calculated values differed by a factor of up to 4.5 and 3, respectively). At present, measurement of the Kapp and ligand purity in the appropriate solution at the desired pH and temperature would seem to be the best strategy to adopt rather than attempting to calculate the constant. Since no recognized international standard exists for [Mg2+] at the micromolar level, values in the literature for Kd, etc. in this range can only be regarded as approximate.

Buffers↗