Biomedical subjects
R J Donnelly
Publications and source records attributed to R J Donnelly.
Oesophageal cancer in Britain.
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Preoperative chemotherapy for cancer of the oesophagus.
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Madura foot of the chest wall; cure after radical excision.
Maduromycosis is a chronic granulomatous condition caused by fungal infection and is rarely encountered in Europe. To our knowledge, this is the first report of a case of maduromycosis affecting the chest wall in the United Kingdom. Conservative excision and drainage of the lesion combined with ketoconazole treatment in a dose 400 mg daily for several months failed to cure the condition. However, radical excision of the lesion combined with myoplastic repair of the defect in the chest wall eradicated the disease. Maduromycosis can occur in the chest wall and should be suspected in the immigrant population from tropical and subtropical areas. We recommend radical resection of similar lesions, combined with prolonged treatment with an antifungal agent e.g. ketoconazole when the causative organism is madurella mycetomis.
Endoscopy assisted microthoracotomy: initial experience.
BACKGROUND: Although thoracoscopy has been used for diagnostic and minor therapeutic procedures for many years, there have been few reports of its use in performing major intrathoracic procedures, which have traditionally required formal thoracotomy. METHODS: Twenty one patients (M:F 1.2:1; mean (SD) age 47.1 (18.8), range 17-75 years) underwent endoscopic intrathoracic surgery. Eight had unidentified peripheral masses on the chest radiograph, eight required lung biopsy, and five had recurrent or persisting pneumothoraces. Under general anaesthesia a laparoscope attached to a video monitor was introduced into the chest. One or two additional stab incisions were made as needed for the introduction of standard surgical or endoscopic instruments and staplers. RESULTS: There were no complications or deaths, though one patient developed a second pneumothorax seven days after endoscopic pleurectomy, necessitating open pleurodesis. All patients were discharged home from two to six days after surgery (mean (SD) 3.7 (1.2) days). CONCLUSION: Endoscopic thoracic surgery is a safe and useful technique for certain cases. It merits further investigation and assessment.
Expandable metal stents for tracheal obstruction: permanent or temporary? A cautionary tale.
An expandable metal stent inserted via a long term tracheostomy successfully relieved life threatening respiratory obstruction due to benign tracheal stenosis. Later the patient's tracheostomy suction catheter became stuck on the stent and dislodged it. The stent was removed electively, without damaging the trachea, with a rigid biopsy forceps.
Retrosternal thyroid.
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Role of salivary epidermal growth factor in the pathogenesis of Barrett's columnar lined oesophagus.
Epidermal growth factor (EGF) is implicated in the regeneration of epithelial cells at the site of inflammation or ulceration in the gastrointestinal tract. Single parotid EGF concentration and production was studied in 64 patients with Barrett's columnar lined oesophagus (CLO), in 22 patients with severe reflux oesophagitis without columnar metaplasia and in 51 normal controls. In control patients, mean salivary EGF concentration was 2790 pg/ml (median 1450 pg/ml; range 450-16,500 pg/ml) and mean single parotid EGF production was 2550 pg/min (median 1750 pg/min; range 790-18,000 pg/min). Patients with severe reflux oesophagitis had a similar EGF concentration (mean 3112 pg/ml; median 1500 pg/ml; range 300-16,000 pg/ml) and production (mean 3100 pg/min; median 2200 pg/min; range 790-17,950 pg/min) to controls. Patients with CLO had a 62 per cent lower mean EGF concentration (mean 1197 pg/ml; median 640 pg/ml; range 233-4500 pg/ml) (P less than 0.001, Mann-Whitney U test) and a 60 per cent lower EGF production (mean 1254 pg/min; median 800 pg/min; range 170-3125 pg/min) (P less than 0.001, Mann-Whitney U test) than patients with severe reflux oesophagitis. A subpopulation with malignant change in CLO (n = 16) had a similar EGF concentration and production to the CLO group as a whole (mean 1240 and 1300 pg/min, respectively). Low salivary EGF levels are associated with Barrett's CLO but not with severe oesophagitis without columnar metaplasia. EGF levels do not identify those patients who will subsequently develop malignant change.
Pain following thoracotomy. A randomised, double-blind comparison of lumbar versus thoracic epidural fentanyl.
Fifty-eight patients scheduled for elective thoracotomy were randomly allocated to receive fentanyl by either the thoracic or the lumbar epidural route for postoperative analgesia. The infusion rate was adjusted to optimise analgesia. Dose adjustment, pain assessment and the incidence of side effects were monitored by a blinded observer at set times over the 24 hour study period. Similar pain scores were obtained in both groups at all assessment times. In addition, there was no significant difference in dose requirements or incidence of side effects between the two groups. There appears little justification for the use of the generally less familiar, and potentially more dangerous, thoracic approach when fentanyl alone is infused into the epidural space following thoracotomy.
Endoscopic bougie and balloon dilatation of multiple bronchial stenoses: 10 year follow up.
This paper reports 10 year follow up data on four patients who underwent mechanical dilatation of multiple bronchial stenoses (sarcoidosis two cases, berylliosis one case, idiopathic stenoses one case). Two patients enjoyed symptomatic and physiological improvement during the nine years before they presented with a recurrence of stenosis. The other two had recurrences sooner, and improved only slightly after they had started prednisolone treatment.
Interleukin-1 stimulates the beta-amyloid precursor protein promoter.
1. Amyloid plaques found in the brains of Alzheimer's diseased patients are composed of the 42 amino acid beta-amyloid peptide (BAP) which is processed out of the larger amyloid precursor protein (APP). 2. To study the regulation of the APP gene expression, we have isolated the promoter region of this angle of this single-copy gene and produced a reporter gene system to determine if the promoter is responsive to agents that may cause the overproduction of APP leading to the abnormal accumulation of plaques in AD. 3. The promoter contains sequences homologous to heat shock elements, AP-1 binding sites, and phorbol ester-inducible sequences as well as GG-rich regions found in other constitutively expressed genes. 4. We show here that this promoter is inducible in cultured cells by interleukin-1 (IL-1) in a transient assay system and that the HSE and AP-1 binding site are required for this inducibility. 5. This induction of transcription from the APP promoter implies that this gene is responsive to tropic and/or trophic agents which may be present in the diseased brain.
Esophagogastrectomy via left thoracophrenotomy.
Esophagogastrectomy is generally considered to be the treatment of choice for resectable tumors of the esophagus. Although many approaches and techniques have been advocated, since April 1983 we have used a left thoracophrenotomy approach for most lesions of the lower two thirds of the esophagus and gastric cardia. Stapling instruments have been used for mobilization of the stomach and fashioning of the esophagogastric anastomosis. One-hundred fifteen patients undergoing resection of malignant tumors with this technique were retrospectively reviewed. Perioperative mortality was 8.7% (10/115). The rate of anastomotic leakage was 1.7% (2/115), and benign narrowing of the anastomosis requiring dilation developed in 16 patients. The rate of recurrent anastomotic tumor was 4.3%. Eighteen patients had complications, and the mean postoperative hospital stay was 13 days. Survival at 3 years was 22.1%. During the period of study, 22 patients underwent esophageal resection by some other approach; the reasons for this are described. The advantages of the left thoracophrenotomy approach are discussed.
Diaphragmatic plication for unilateral diaphragmatic paralysis: a 10-year experience.
Unilateral paralysis of the diaphragm due to nonmalignant disease is an uncommon disorder previously thought to have benign implications. Some patients, however, experience dyspnea and orthopnea with impairment of pulmonary function. Unilateral diaphragmatic plication was performed on 17 patients (16 men and 1 woman with a mean age of 53.7 years [range, 28 to 74 years]) during the last 10 years. Preoperatively each patient was shown to have paradoxical movement of the paralyzed diaphragm on sniffing and to have a reduction in forced vital capacity and lung volumes. These reductions were greater when the patient was in the supine position. All patients had moderate hypoxemia (mean arterial oxygen tension, 73.1 +/- 10.9 mm Hg). Plication was performed by imbricating the diaphragm in layers through a thoracotomy incision. After plication, all patients showed both subjective and objective improvement. Six patients were reassessed 5 or more years after plication (range, 5 to 7 years), and the improvement was maintained. Diaphragmatic plication is a safe and effective procedure for adult patients with dyspnea due to unilateral diaphragmatic paralysis; furthermore, the initial improvement is maintained.
Complications after esophagogastrectomy using stapling instruments.
We studied 195 patients undergoing esophageal resection using stapling instruments during a period of over 8.5 years. Of these, 178 (91.2%) underwent operation for malignant disease. Operative death occurred in 19 patients (9.7%). Nine (4.6%) postoperative complications, excluding stricture formation, were related to the use of stapling instruments, including two operative deaths (1.0%). Anastomotic leaks and gastrotomy staple line leaks were the most common complications (four each). In 7 patients (3.6%) the circular stapler tore the esophagus; anastomotic leaks subsequently developed in 43% of these patients. After we began oversewing gastrotomy staple lines in 1984, we experienced only one gastrotomy leak due to a technical error. Postoperative stricture formation occurred soon after resection and responded well to one or two dilations. It is better to err on the side of choosing too small a stapling head when performing an esophageal anastomosis because this may reduce the incidence of leaks, and further strictures are easily dealt with.
Thoracoscopy: a review of 121 consecutive surgical procedures.
The records of 121 patients who underwent surgical thoracoscopy between 1976 and 1987 were reviewed. The indications for thoracoscopy were pleural effusion (88%), pleural thickening (7.4%), and a mass on the chest roentgenogram (15%). All procedures were performed under general anesthesia with a rigid thoracoscope and 91 patients (75%) were diagnosed as having a malignant process. Although thoracotomy was undertaken in 20 patients (16.5%), no patient with benign disease underwent diagnostic thoracotomy. Thoracoscopy had a 98.9% sensitivity and a 93.3% specificity in this series. One patient died of a myocardial infarction after the procedure, and 11 patients (9.1%) had other, predominantly respiratory, complications. We confirm that surgical thoracoscopy is a useful procedure in the diagnosis of pleural processes.
Recent surgical experience for pulmonary tuberculosis.
Lung resection for pulmonary tuberculosis is unusual today. Over a 10-year-period 31 patients with pulmonary tuberculosis underwent thoracotomy at this Regional Centre. Five of these were for complications of known tuberculosis; two subsequently proved to be complications of pulmonary tuberculosis, and the remainder were for suspected malignancy. The clinical features, radiology, microbiology, and pathology are reviewed and the contemporary role of the surgeon in the management of pulmonary tuberculosis is examined.
Interleukin 1 regulates synthesis of amyloid beta-protein precursor mRNA in human endothelial cells.
We have analyzed the modulation of amyloid beta-protein precursor (APP) gene expression in human umbilical vein endothelial cells (HUVEC). The level of the APP mRNA transcripts increased as HUVEC reached confluency. In confluent culture the half-life of the APP mRNA was 4 hr. Treatment of the cells with human-recombinant interleukin 1 (IL-1), phorbol 12-myristate 13-acetate, or heparin-binding growth factor 1 enhanced the expression of APP gene in these cells, but calcium ionophore A23187 and dexamethasone did not. The protein kinase C inhibitor 1-(isoquinolinsulfonyl)-2-methylpiperazine (H7) inhibited IL-1-mediated increase of the level of APP transcripts. To map IL-1-responsive elements of the APP promoter, truncated portions of the APP promoter were fused to the human growth hormone reporter gene. The recombinant plasmids were transfected into mouse neuroblastoma cells, and the cell medium was assayed for the human growth hormone. A 180-base-pair region of the APP promoter located between position -485 and -305 upstream from the transcription start site was necessary for IL-1-mediated induction of the reporter gene. This region contains the upstream transcription factor AP-1 binding site. These results suggest that IL-1 upregulates APP gene expression in HUVEC through a pathway mediated by protein kinase C, utilizing the upstream AP-1 binding site of the APP promoter.
Oesophagogastrectomy in patients over 70.
Although the results of oesophageal resection for benign and malignant disease are well documented, the risk of operative death and long term survival in patients over the age of 70 is not well defined. The outcome has been reviewed for 46 patients (23 male, 23 female) aged 70 years or more (mean 74 years) undergoing oesophageal resection during a period of seven years; 16 patients were 75 years or over. All resections were performed with the EEA stapler, except for one cervical anastomosis that was stitched by hand. In 42 patients resection was for malignancy. Six patients died within 30 days of operation or during the initial hospital stay, giving an operative mortality of 13%. Only one of the 16 patients aged 75 years or more died. Cardiopulmonary complications accounted for most of the operative deaths. Patients were scored retrospectively by a multifactual risk factor. Patients who left hospital had a mean preoperative score of 3.66, compared with 15.2 for those who died. Use of such a score may help to improve selection for surgery in this age group. It is concluded that oesophagogastrectomy may be performed in selected patients over the age of 70 years with acceptable mortality, morbidity, and length of hospital stay.