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Biomedical subjects

C J Hilton

Publications and source records attributed to C J Hilton.

At least 19 recordsLinked to original sources
PubMed2001

Anti-peptide antibody blocks peptide binding to MHC class I molecules in the endoplasmic reticulum.

The finding that MHC class I molecules are physically associated with the TAP transporter has suggested that peptides may be directly transported into the binding groove of the class I molecules rather than into the lumen of the endoplasmic reticulum (ER) where they subsequently would encounter class I molecules by diffusion. Such a mechanism would protect peptides from peptidases in the ER and/or escaping back into the cytoplasm. However, we find that an anti-peptide Ab that is cotranslationally transported into the ER prevents TAP-transported peptides from being presented on class I molecules. The Ab only blocks the binding of its cognate peptide (SIINFEKL) but not other peptides (KVVRFKDL, ASNENMETM, and FAPGNYPAL). Therefore, most TAP-transported peptides must diffuse through the lumen of the ER before binding stably to MHC class I molecules.

ATP-Binding Cassette Transporters↗
PubMed2001

Emergency management of aorto-bronchial fistula after implantation of a self-expanding bronchial stent.

We report a case of aorto-bronchial fistula 7 years after implantation of a self-expanding metal stent into the left main bronchus. The clinical presentation was characterised by left-sided chest pain, dyspnea and a single bout of haemoptysis. The fistula was surgically managed by aortic resection and primary repair of the aorta, and patch repair of the left main bronchus over a Polyflex covered bronchial stent. When haemoptysis occurs in a patient with a history of bronchial stent implantation, the presence of an aorto-bronchial fistula should be considered. Early diagnosis offers the only possibility of recovery through a lifesaving surgical procedure.

Adult↗
PubMed2000

Effects of surgery for postinfarction ventricular tachycardia on parameters of left ventricular function.

Heart failure is the leading cause of death in patients after surgery for ventricular tachycardia. This study examines the effects of antiarrhythmic surgery on 4 parameters of left ventricular (LV) function. Global ejection fraction, segmental wall motion score, homogeneity of contraction, and diastolic function were measured in 32 patients by technetium-99m radionuclide ventriculography. Ejection fraction was measured from the left anterior oblique image. Wall motion score was assessed semiquantitatively for 11 LV segments from 3 projections. Homogeneity of contraction was expressed as the SD of the LV phase analysis curve during systole from the left anterior oblique image. Diastolic function was expressed in terms of peak and mean first time derivative of the action potential (dV/dt) of the LV function curve. Subgroup analyses were performed to distinguish the effects of aneurysmectomy, coronary artery bypass grafting, and changes in angiotensin converting enzyme inhibitor therapy. Mean systolic function improved after surgery (ejection fraction 22% vs 32%, p <0001; wall motion score 20 vs 13, p <0.0001; phase analysis 18 vs 12, p <0.03). Mean diastolic function also improved (peak dV/dt 0.83 +/- 0.32 vs 1.49 +/- 0.39, p = 0.006; mean dV/dt 0.41 +/- 0.15 vs 0.76 +/- 0.27, p = 0.006). Improvements were not confined to those who had aneurysmectomy or coronary bypass grafting and were not explained by changes in vasodilator therapy. Thus, antiarrhythmic surgery does not inherently damage LV function. Significant improvements were observed in most patients. Failure to improve indicated a poor longer term prognosis.

Aged↗
PubMed2000

Management of complications of tracheal surgery--a case of dehiscence.

We report a case of tracheal stenosis in a patient with immune thrombocytopenia who presented 4 yr after splenectomy. The 20-yr progression of the stenosis and management, including resection, is charted. The period after resection was complicated by wound infection, surgical emphysema, mediastinitis and dehiscence of the anastomosis of the trachea. The management of patients with tracheal lesions is discussed, but concentrates on airway care after tracheal resection when complications developed. A laryngeal mask airway was used to stabilize an uncuffed tracheal tube at the site of dehiscence.

Adult↗
PubMed1999

Identifying patients at low risk of death from cardiac failure after operation for postinfarct ventricular tachycardia.

BACKGROUND: In unselected patients, cardiac failure accounted for most deaths after antiarrhythmic operation (ER) for postinfarction ventricular tachycardia (VT). This study aimed to determine whether patients at low risk of this outcome could be predicted from a retrospective analysis of variables from 100 consecutive ER patients. METHODS: Thirteen variables suggested by other researchers as predictive of outcome were analyzed. At the time of study, ER was the only therapy available for drug refractory VT. RESULTS: Only emergency ER, wall motion score less than 3 and Killip classification were significantly related to death from cardiac failure. The lack of correlation between emergency ER and variables of ER timing, VT less than 24 hours of ER or VT type implies that the need for emergency ER is also related to ventricular dysfunction. Multivariate analysis identified a group at particularly low risk of death with a specificity of 95%. CONCLUSIONS: Patients at low risk of death after ER can be identified prospectively. In the implantable cardioverter defibrillator era, elective ER is best reserved for such patients. Emergency ER may still be justified in younger patients without comorbidity who will die of VT without it.

Adolescent↗
PubMed1999

Surgery for postinfarction ventricular tachycardia in the pre-implantable cardioverter defibrillator era: early and long term outcomes in 100 consecutive patients.

OBJECTIVE: To report outcome following surgery for postinfarction ventricular tachycardia undertaken in patients before the use of implantable defibrillators. DESIGN: A retrospective review, with uniform patient selection criteria and surgical and mapping strategy throughout. Complete follow up. Long term death notification by OPCS (Office of Population Censuses and Statistics) registration. SETTING: Tertiary referral centre for arrhythmia management. PATIENTS: 100 consecutive postinfarction patients who underwent map guided endocardial resection at this hospital in the period 1981-91 for drug refractory ventricular tachyarrhythmias. RESULTS: Emergency surgery was required for intractable arrhythmias in 28 patients, and 32 had surgery within eight weeks of infarction ("early"). Surgery comprised endocardial resections in all, aneurysmectomy in 57, cryoablations in 26, and antiarrhythmic ventriculotomies in 11. Twenty five patients died < 30 days after surgery, 21 of cardiac failure. This high mortality reflects the type of patients included in the series. Only 12 received antiarrhythmic drugs after surgery. Perioperative mortality was related to preoperative left ventricular function and the context of surgery. Mortality rates for elective surgery more than eight weeks after infarction, early surgery, emergency surgery, and early emergency surgery were 18%, 31%, 46%, and 50%, respectively. Actuarial survival rates at one, three, five, and 10 years after surgery were 66%, 62%, 57%, and 35%. CONCLUSIONS: Surgery offers arrhythmia abolition at a risk proportional to the patient's preoperative risk of death from ventricular arrhythmias. The long term follow up results suggest a continuing role for surgery in selected patients even in the era of catheter ablation and implantable defibrillators.

Aneurysm↗
PubMed1998

Orthotopic cardiac transplantation for the failing Fontan circulation.

OBJECTIVE: Modified Fontan procedures are now employed in several conditions unsuitable for bi-ventricular repair. Selection criteria have been relaxed. The procedure is palliative. Longterm outlook is unknown. This study evaluated factors associated with the development of a failing Fontan circulation and transplantation results. METHODS: Retrospective review of patients referred to a single centre for cardiac transplant assessment. RESULTS: Between 1985 and 1996, 46 of 448 cardiac transplants were performed for congenital heart disease. Nine of these were performed in patients with a failing Fontan circulation (four adults, five children). In six cases, the dominant ventricle had left ventricular (LV) morphology. Congenital anomalies included double outlet right ventricle (three cases), double inlet left ventricle (two cases), tricuspid atresia (two cases), and pulmonary atresia with intact ventricular septum (one case). Fontan procedures were performed in absence of sinus rhythm (four cases), atrio-ventricular (AV) valve regurgitation (two cases), aortic regurgitation and systolic LV dysfunction (one case), elevated mean pulmonary artery pressure (one case), and older age (>7 years, eight cases). Three patients required early re-operation and two needed permanent pacing. Subsequent deterioration associated with loss of sinus rhythm (four cases) and progressive AV valve regurgitation (seven cases) led to transplant assessment (at < 1 year, five cases; at 2-12 years, four cases). All patients were listed for transplantation. Three patients required intravenous inotropic support and three patients with lymphocytotoxic antibodies needed prospective crossmatching. Donor cardiectomy was modified to facilitate implantation. The recipient operation involved pulmonary artery reconstruction (using pericardium), modified atrial and direct caval anastomoses. Three patients died within 24 h of surgery (two graft failures, one haemorrhage). In operative survivors (n = 6), intensive care stay was 3-16 days, and hospital stay ranged from 14 to 32 days. There have been no subsequent deaths (follow up, 0.5-4.7 years). CONCLUSION: In high-risk Fontan candidates, transplantation may be preferable at the outset. Previous surgery, lymphocytotoxic antibodies, indeterminate pulmonary vascular resistance, emergency status, sub-optimal donor selection, and perioperative bleeding contribute to peri-operative mortality. In survivors, the outcome remains very encouraging.

Antilymphocyte Serum↗
PubMed1997

Right ventricular disarticulation procedures: the role of late potentials in the genesis of postoperative ventricular arrhythmias.

Arrhythmogenic right ventricular disease may be associated with life-threatening and drug refractory ventricular arrhythmias. Right ventricular disarticulation procedures are effective antiarrhythmic surgical approaches in selected patients. This study examined the role of late potentials in the postoperative development of new ventricular arrhythmias, and showed that right ventricular isolation is effective, probably because it destroys the tissue giving rise to late potentials. Total disarticulation is associated with fewer postoperative arrhythmias than partial isolation procedures. Total disarticulation may be the surgical approach of choice in such patients.

Adult↗
PubMed1997

Adrenocorticotropin-secreting carcinoid tumour identified and treated 12 years after presentation with Cushing's syndrome.

A case of Cushing's syndrome due to an adrenocorticotropin (ACTH) secreting bronchial carcinoid tumour is described. Endocrine assessment suggested ectopic ACTH syndrome, but imaging revealed no tumour. Bilateral adrenalectomy was performed, and computed tomographic scans of chest and abdomen were performed annually. A small nodule became apparent in the right lung 12 years after the presentation, which postoperatively was confirmed as the bronchial carcinoid tumour responsible for the ectopic ACTH syndrome.

ACTH Syndrome, Ectopic↗
PubMed1996

Vascular complications of lung transplantation.

BACKGROUND: The data on vascular anastomotic complications after single-lung and bilateral lung transplantation are scant. METHODS: We reviewed the data on our patients having single and bilateral lung transplantation to examine our experience and management of vascular anastomotic complications. RESULTS: We retrospectively identified 5 of 109 consecutive patients undergoing lung transplantation who had postoperative pulmonary arterial or venous obstruction. There were 4 women and 1 man (age range, 32 to 53 years). Three patients had left single-lung transplantation, 1 patient had right single-lung transplantation, and 1 patient underwent bilateral sequential lung transplantation. Complications comprised two right-sided and two left-sided pulmonary artery stenoses and one combined left pulmonary arterial and venous obstruction. Isotope perfusion scanning was used in 3 patients and suggested a vascular stenosis in all of them. Pulmonary angiography was used in each as a confirmatory test and to demonstrate anatomic details. Transesophageal echocardiography was used in 1 patient and did not detect a right pulmonary artery stenosis. One patient underwent revision of a pulmonary artery stenosis with a period of warm ischemia and subsequent fatal lung injury. Two revisions were undertaken on cardiopulmonary bypass with a cold blood flush to the transplanted lung. One venous anastomotic angioplasty with stent insertion was performed. Two patients died before treatment. All 5 patients died between 5 and 630 days postoperatively. CONCLUSIONS: Vascular complications carry a high mortality. Reoperation, preferably using cardiopulmonary bypass and a cold blood flush technique to avoid further lung injury, is recommended. In high-risk patients, dilation or stent insertion can be considered.

Adult↗
PubMed1996

Healing of the bronchus in pulmonary transplantation.

OBJECTIVE: To review the results of bronchial healing in a consecutive series of 100 isolated pulmonary transplants, performed at one centre between 1987 and 1994. METHODS: A retrospective review of 123 assessable bronchi (61 in single lung and 62 in bilateral lung) transplants was carried out. All anastomoses were assessed by bronchoscopy at 7-10 days, and follow up was from one to seven years. The effect on bronchial dehiscence or stenosis requiring endobronchial stent, of suture technique, pre and post operative steroid administration, bronchial wrap, donor ischaemic time and time to first rejection episode was assessed. RESULTS: Complications of airways healing occurred in four patients: stenosis in two and dehiscence in two (1.6% of bronchi at risk in both groups). Airway complication was not affected by steroids, pre-operative diagnosis, presence of a wrap (34 with pericardium or omentum, 89 with peribronchial tissue alone) or any other variable. There was a higher incidence of dehiscence (2/36) with continuous rather then interrupted (0/87) suture, but this was not statistically significant. There was one airway-related death. Two patients who required anastomotic stenting remain alive and well. CONCLUSIONS: A very low complication rate can be achieved without recourse to bronchial wrapping, telescoping anastomoses or steroid avoidance. Combined heart-lung transplantation or bronchial revascularisation are not required to achieve reliable bronchial healing.

Adolescent↗
PubMed1995

Mechanical ventricular assistance for the failing right ventricle after cardiac transplantation.

Right ventricular failure secondary to elevated pulmonary vascular resistance (PVR) following orthotopic cardiac transplant is a complication with a high mortality; and patients with high resistance are often not accepted on transplant waiting lists. We describe six cases of right ventricular failure after cardiac transplant managed by right ventricular assist device (RVAD), four of whom died and two patients who survived following life-threatening complications.

Adult↗
PubMed1995

Nonischemic ventricular tachycardia: surgical or medical treatment?

Fifty-two consecutive patients with nonischemic ventricular tachycardia (VT) were seen between 1985 and 1991. Twenty-two patients underwent surgery, while in the remaining 30, the VT was well controlled on medication. In the surgical group, arrhythmogenic right ventricular dysplasia (ARVD) was the cause of VT in 12 patients, cardiomyopathy (CM) in 6, posttetralogy of Fallot repair in 2, myocarditis in 1, and myocardial hamartoma in 1. The mean number of drugs tried and found ineffective was 5.5. There were three early deaths; 13 patients are symptom-free without taking any medication. In the medical group, the pathology associated with the VT was myocarditis in 2 patients, CM in 11, and ARVD in 2. In ten patients, VT appeared idiopathic, 1 was exercise-induced, 3 were catecholamine sensitive, and 1 presented with long QT syndrome. Beta blockers controlled the symptoms in 43% of the patients, amiodarone in 20%, and flecainide in 17%. The mortality was higher in the surgical group, but 95% of them are VT-free, compared with those on medical treatment (55%) over the last 8 years' follow-up. In conclusion, the nonischemic VT is a serious condition. Medical therapy is usually effective, but if it fails, VT surgery should be considered.

Adolescent↗
PubMed1995

Bilateral sequential lung transplantation for end stage septic lung disease.

BACKGROUND: Bilateral sequential lung transplantation (BSLT) has been widely adopted as an alternative to combined heart and lung transplantation for the management of end stage septic lung disease in many transplant centres. METHODS: A retrospective review was undertaken of the first 32 consecutive patients with septic lung disease to undergo BSLT at the Freeman Hospital. RESULTS: Between April 1988 and October 1994 32 patients underwent BSLT. Survival at 30 days was 85% and actuarial survival at one year was 70%. Improved pulmonary function was seen in all surviving patients. CONCLUSION: BSLT for septic lung disease offers comparable survival to heart-lung transplantation, with excellent functional results. Long term results may be superior because the disadvantages of transplanting the heart are avoided.

Adolescent↗
PubMed1995

Conserved region of the cytoplasmic domain is not essential for erythropoietin-dependent growth.

Recent studies have suggested that the membrane proximal region of the cytoplasmic domain of the erythropoietin receptor and other members of the cytokine receptor superfamily may be required for signal transduction. Expression of several deletion mutants of the erythropoietin receptor in Ba/F3 cells showed that a region with homology to the interleukin-2 receptor beta-chain which includes Box 2 is not essential for erythropoietin-dependent cell proliferation. However, a region between Box 1 and Box 2 contains essential residues for proliferative response. Expression of mutant receptors was confirmed by reverse transcriptase-PCR analysis and by Western blotting, which also showed no evidence for expression of endogenous wild-type receptor. These findings are in direct conflict with previously reported mutagenesis studies of the erythropoietin receptor suggesting that mitogenesis may be channelled through more than one pathway depending on the complement of signaling molecules expressed in the cell.

Amino Acid Sequence↗
PubMed1994

Airway complications after pulmonary transplantation.

Airway healing was identified initially as one of the fundamental limitations of pulmonary transplantation. Recent experience suggests that this is no longer the case. A series of 67 pulmonary transplants (27 heart-lung, 31 single-lung, 9 double-lung) in 66 patients surviving more than 14 days was reviewed with reference to airway complications. There were 75 anastomoses at risk in two groups as defined by anastomotic location: 47 anastomoses in 38 patients in a bronchial group and 28 anastomoses in 28 patients in a tracheal group. A total of 10 airway complications developed (stenosis in 5 patients [4 bronchial group, 1 tracheal group] and dehiscence in 5 patients [1 bronchial group, 4 tracheal group]) causing two airway-related deaths (2 of 67) in the series. However, no significant correlation could be identified with either ischemic interval, suture technique, type of wrap, preoperative or postoperative steroid therapy, or date of first rejection episode. Airway complications are no longer a major limitation of pulmonary transplantation. Satisfactory airway healing can occur in both the presence of steroid therapy and the absence of an omental or pericardial wrap.

Adolescent↗
PubMed1994

Outcome of Toxoplasma gondii mismatches in heart transplant recipients over a period of 8 years.

Donor-related infection due to Toxoplasma gondii is a well-recorded complication of cardiac transplantation. In order to assess the efficacy of co-trimoxazole in small doses as prophylaxis for primary Toxoplasma gondii infection in seronegative heart and heart-lung transplant recipients receiving organs from seropositive donors, we reviewed the serostatus and clinical outcome of all such mismatched transplants performed at our unit over a period of 8 years. Of 310 transplants performed between May 1985 and May 1993, donor and recipient serum samples were available for 257 heart and 33 heart-lung transplants. Of these, 13 (4.5%) were toxoplasma mismatches. Post-transplant review serum samples were available for 3 months or longer for nine of the 13 mismatches. The first three patients received co-trimoxazole 480 mg bd orally for 3 months (regimen A) while the remainder received only the standard prophylaxis designed for Pneumocystis carinii i.e., 960 mg bd orally three times per week for 3 months (regimen B). Seroconversion was demonstrated in only one patient (regimen A). Furthermore, none of the mismatched patients developed serious infection compatible with primary toxoplasmosis. We therefore conclude that in centres with a low prevalence of toxoplasma seropositivity, testing of donor and recipient serum for Toxoplasma gondii antibody should be performed only when clinically indicated and, in addition, standard prophylaxis for Pneumocystis carinii may be adequate for preventing primary toxoplasmosis.

Adolescent↗