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Biomedical subjects

J P McGoldrick

Publications and source records attributed to J P McGoldrick.

At least 19 recordsLinked to original sources

Does hypothermia prevent cerebral ischaemia during cardiopulmonary bypass?

It is believed that moderate hypothermia (25-32 degrees C) during cardiopulmonary bypass provides cerebral protection by reducing the cerebral metabolic rate (CMRO2). Nevertheless episodes of ischaemia do occur and thus it has been suggested that cerebral oxygenation should be monitored by jugular venous oximetry. However, this technique is cumbersome and invasive. Near infrared spectroscopy (NIRS) provides a non-invasive assessment of cerebral oxygenation and this was used together with continuousjugular venous oximetry in 21 patients undergoing hypothermic cardiopulmonary bypass. During the hypothermic period, jugular venous oximetry indicated reduced oxygen extraction consistent with a reduction in CMRO2 (increase from 61 +/- 2.5% to 74 +/- 2.5%). In contrast, near infrared spectroscopy demonstrated increased oxygen extraction (HbO2 - 11.5 +/- 1 microM, HHb + 3.2 +/- 0.3 microM) and a fall in the cerebral concentration of oxidized cytochrome oxidase ( - 1.7 +/- 0.3 microM) indicating ischaemia. These results suggest that cerebral ischaemia occurs during hypothermic cardiopulmonary bypass with a spurious rise in jugular venous oxygen saturation, which represents arterio-venous shunting. Thus if hypothermia does facilitate cerebral protection it does not appear to be a direct result of a reduction in CMRO2 and oxygen requirement.

Adult↗

Haemolysis during cardiopulmonary bypass: an in vivo comparison of standard roller pumps, nonocclusive roller pumps and centrifugal pumps.

Cardiopulmonary bypass (CPB) involves the use of either an occlusive roller pump or centrifugal pump. Damage to blood elements, including haemolysis, may arise from occlusion when using a roller pump; the appropriate degree of occlusion has not yet been determined scientifically. Centrifugal and nonocclusive roller pumps are reputed to reduce haemolysis. The objective of this study was to compare haemolysis caused by a standard roller pump with a dynamically set nonocclusive roller pump and with a centrifugal pump. We prospectively randomized 60 patients undergoing routine coronary artery surgery into three groups: standard roller pump (STD, n = 20), dynamically set roller pump (DYN, n = 20), or centrifugal pump (CEN, n = 20). The level of plasma free haemoglobin (FHb) was measured preoperatively, and the rate of formation of FHb (in mg/dl/min) was determined at the end of the ischaemic phase and at the end of CPB. Cardiotomy suction blood was isolated for the ischaemic phase and returned before the end of CPB. It was found that there were no differences between the groups in demographic or operative variables. The rate of formation of FHb at the end of the ischaemic phase was similar for all groups (STD 0.108 +/- 0.10, DYN 0.117 +/- 0.08, CEN 0.129 +/- 0.07). At the end of CPB, after return of the cardiotomy suction blood, there was a significant (< 0.001) increase in the rate of formation of FHb in all groups. The increase was similar for each of the groups (STD 0.424 +/- 0.17, DYN 0.481 +/- 0.20, CEN 0.471 +/- 0.18). We conclude that the rates of haemolysis are similar for each of the pump types, and no benefit is conferred by the use of either a dynamically set roller pump or a centrifugal pump compared with the standard roller pump. The return of the cardiotomy suction blood to the circulation is the principal source of plasma free haemoglobin.

Aged↗

Enhancing liver blood flow after cardiopulmonary bypass: the effects of dopamine and dopexamine.

Liver blood flow is reduced after cardiopulmonary bypass (CPB) and both dopamine and dopexamine are used to overcome this. This study compares the effects of these agents on liver blood flow. Thirty patients undergoing elective coronary artery bypass graft surgery were randomized into three groups (n = 10 per group). Six hours after surgery baseline liver blood flow was determined by the percentage disappearance rate of indocyanine green measured by dichromatic auricular densitometery. Patients then received infusions of either: (1) placebo (dextrose 5%); (2) dopamine (4 micrograms/kg/min); (3) dopexamine (1 microgram/kg/min increasing to 2 micrograms/kg/min). One hour after infusion, liver blood flow measurements were repeated. In the dopexamine group the infusion was increased and the measurements repeated another hour later. We found that patient-specific variables and operative details were similar for all groups. Postoperative cardiac index and heart rate were increased significantly by dopamine (cardiac index 2.82 +/- 0.46 l/m/m2 vs 3.28 +/- 0.67 l/m/m2: p < 0.001 and heart rate 87.5 +/- 13.2 vs 96 +/- 16: p < 0.05) and dopexamine at 2 micrograms/kg/min (cardiac index 2.71 +/- 0.53 l/m/m2 vs 3.45 +/- 0.67 l/m/m2: p < 0.05 and heart rate 89.0 +/- 18.9 vs 107.4 +/- 13.6: p < 0.001) compared to placebo (cardiac index 2.97 +/- 0.8 l/m/m2 vs 3.18 +/- 0.9 l/m/m2: p > 0.05 and heart rate 77.2 +/- 7.4 vs 77.3 +/- 8: p > 0.05) despite similar atrial and systemic arterial pressures. The disappearance rate of indocyanine green was not altered during infusion of placebo group (9.0 +/- 3.2%/min vs 7.9 +/- 3.0%/min: p > 0.05) or dopexamine at 1 microgram/kg/min (9.7 +/- 3.1%/min vs 11.2 +/- 4.1%/min: p > 0.05). The disappearance rate was increased with dopamine (6.7 +/- 3.7%/min vs 11.8 +/- 3.0%/min: p < 0.05) and dopexamine 2 micrograms/kg/min (9.7 +/- 3.1%/min vs 13.5 +/- 3.2%/min: p < 0.05). This indicates a 76% increase in liver blood flow with dopamine and a 38% increase with dopexamine. We conclude that dopamine 4 micrograms/kg/min and dopexamine 2 micrograms/kg/min increase liver blood flow, although this may, in part, be related to an increase in cardiac output. Dopexamine shows no advantage over dopamine in enhancing liver blood flow after CPB.

Aged↗

Characterization of a mammalian homolog of the Escherichia coli MutY mismatch repair protein.

A protein homologous to the Escherichia coli MutY protein, referred to as MYH, has been identified in nuclear extracts of calf thymus and human HeLa cells. Western blot (immunoblot) analysis using polyclonal antibodies to the E. coli MutY protein detected a protein of 65 kDa in both extracts. Partial purification of MYH from calf thymus cells revealed a 65-kDa protein as well as a functional but apparently degraded form of 36 kDa, as determined by glycerol gradient centrifugation and immunoblotting with anti-MutY antibodies. Calf MYH is a DNA glycosylase that specifically removes mispaired adenines from A/G, A/7,8-dihydro-8-oxodeoxyguanine (8-oxoG or GO), and A/C mismatches (mismatches indicated by slashes). A nicking activity that is either associated with or copurified with MYH was also detected. Nicking was observed at the first phosphodiester bond 3' to the apurinic or apyrimidinic (AP) site generated by the glycosylase activity. The nicking activity on A/C mismatches was 30-fold lower and the activity on A/GO mismatches was twofold lower than that on A/G mismatches. No nicking activity was detected on substrates containing other selected mismatches or homoduplexes. Nicking activity on DNA containing A/G mismatches was inhibited in the presence of anti-MutY antibodies or upon treatment with potassium ferricyanide, which oxidizes iron-sulfur clusters. Gel shift analysis showed specific binding complex formation with A/G and A/GO substrates, but not with A/A, C.GO, and C.G substrates. Binding is sevenfold greater on A/GO substrates than on A/G substrates. The eukaryotic MYH may be involved in the major repair of both replication errors and oxidative damage to DNA, the same functions as those of the E. coli MutY protein.

Amino Acid Sequence↗

Combined oesophageal adenocarcinoma and carcinoid in Barrett's oesophagitis: potential role of enterochromaffin-like cells in oesophageal malignancy.

A case of combined adenocarcinoma and carcinoid tumour which occurred in a patient with a Barrett's oesophagus is presented. Its significance is discussed in relation to the potential role of enterochromaffin-like cells in the development of oesophageal malignancy, and the possibility is raised that long term treatment with omeprazole, commonly used in this condition, could promote this.

Adenocarcinoma↗

Type 1 aortic dissection with right coronary artery occlusion and fistula to right atrium and right ventricle.

A fistula between the aorta and right atrium which communicates with the right ventricle is an extremely rare and rapidly lethal complication of aortic dissection. There are only three previously reported cases of survival after operative repair of aorto-right atrial fistulae in the literature. We describe a patient who experienced acute aortic dissection with fistula formation to the right atrium and to the right ventricle. The patient underwent successful operative repair.

Aortic Dissection↗

Herpes simplex virus infection in heart-lung transplant recipients.

We report our experience of herpes simplex virus infection in a series of 51 recipients of heart lung transplantation (HLT). Nine patients, all of whom were seropositive for the virus preoperatively, developed HSV infection. Seven episodes of culture-proved mucocutaneous HSV infection without evidence of pulmonary involvement occurred in four patients. Six episodes of HSV pneumonia were seen in a further five patients, one of whom died. Diagnosis of HSV pneumonia was by histological appearances on transbronchial biopsy, together with culture of lung tissue or bronchoalveolar lavage. Concomitant cytomegalovirus infection occurred in four patients. All patients who developed HSV pneumonia did so within the first two postoperative months; in four patients following augmented immunosuppression. We now suggest that HLT recipients who are HSV antibody-positive should receive prophylactic acyclovir for the first two months after surgery and at times of augmented immunosuppression.

Acyclovir↗

Early graft function following heart and lung transplantation.

Fifty-one patients underwent heart-lung transplantation between April 1984 and October 1988. The first five donor organs were removed in an adjacent operating theatre. Organs were subsequently removed from distant centres. The method of preservation consisted of cold cardioplegic arrest of the heart using St. Thomas' solution, followed by a simple, cold pulmonary artery flush of a lung perfusate developed at Papworth Hospital. Administration of the solution was preceded by an infusion of prostacyclin into the pulmonary artery during preliminary dissection of the donor organs. The total ischaemic time ranged from 48 to 51 min (mean 49.6 min) for the near procurement group and from 70 to 249 min (mean 154.2 min) for the distant procurement group. There were no primary organ failures. Function of the lungs was assessed by gas exchange, pulmonary function tests, time to extubation, and survival data. Serial radiological studies were used to monitor graft performance in the postoperative period. We report here on our clinical experience of early graft function following heart and lung transplantation.

Adolescent↗

Early experience of heart-lung transplantation.

We report our experience of heart-lung transplantation for the treatment of children with terminal respiratory disease. Between May 1987 and October 1988 we performed heart-lung transplantation in five children under the age of 16 (age range 11-15). All the patients were severely disabled by dyspnoea and hypoxia. Two had primary pulmonary hypertension, two cystic fibrosis, and one had Eisenmenger's syndrome. All five children are alive and well five to 17 months after operation and have returned to activities normal for their age. Three of the five patients had episodes of infection after operation. These were staphylococcal pneumonia, herpes simplex pneumonitis and, in one of the patients with cystic fibrosis, persistent purulent sputum. The mean number of episodes of rejection per child was 2.7 per half year. Heart-lung transplantation is a practical treatment for children in these disease groups with terminal respiratory failure.

Adolescent↗

Coarctation of aorta: late aneurysm formation with Dacron onlay patch grafting.

Repair of coarctation of the aorta using Dacron onlay patch grafting performed in a 2 1/2-year-old child, with subsequent late formation of a true aneurysm on the side of the graft, is reported. Review of the literature did not reveal other cases of late formation of true aneurysm on the side of the Dacron onlay patch graft.

Aortic Aneurysm↗

Two decades' experience with aortic valve replacement with pulmonary autograft.

Aortic valve replacement with a pulmonary autograft was performed on 241 patients between June 1967 and October 1986 at National Heart Hospital, Guy's Hospital, Middlesex Hospital, Harley Street Clinic, and Italian Hospital in London by one of the authors (D.N.R.). The longest follow-up is 18 years 7 months, and the cumulative total follow-up is 1130 patient-years (pt-yr). The overall 30-day mortality rate is 6.6% (16 patients), with no deaths after 1976, and the late mortality rate is 1.7%/pt-yr (19 patients). The actuarial survival rate is 57.3% +/- 9.6% at 19 years. No anticoagulation has been used and there have been no thromboembolic episodes. The incidence of bacterial endocarditis is 1.2%/pt-yr (14 patients), and its actuarial event-free rate is 74.2% +/- 8.1% at 19 years. Reoperation because of failure of the pulmonary autograft was performed on 36 patients, 27 of whom needed valve replacement. The incidence of pulmonary autograft replacement is 2.5%/pt-yr, and its actuarial event-free rate is 48.5% +/- 13.7% at 19 years. For reconstruction of the right ventricular outflow tract, 186 aortic homografts, 26 pulmonary homografts, 16 autologous fascia lata valved conduits, 7 autologous pericardial conduits with or without a valve, and 6 xenograft valved Dacron conduits were used. Thirty-one patients were reoperated on, mostly because of degeneration of this material. Pulmonary rather than aortic homografts are now favored for reconstruction of the right ventricular outflow tract Because of its satisfactory long-term result without the need for anticoagulation, as well as its safety as an established surgical procedure, this operation can be recommended to a wider range of patients.

Actuarial Analysis↗