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Biomedical subjects

D Cunningham

Publications and source records attributed to D Cunningham.

At least 235 records · Page 13Linked to original sources
PubMed1990

Aromatase inhibition in advanced prostatic cancer: preliminary communication.

We report the results of the first use of a steroidal aromatase inhibitor, 4-hydroxyandrostenedione (4-OHA, CGP 32349), in the palliation of patients with advanced, hormone resistant, prostatic cancer. Twelve of 19 patients (63%), who had relapsed following castration and other therapies, gained significant pain relief following weekly intramuscular injections of 4-OHA. Five patients (31%) experienced a transient 'tumour flare', represented by an increase in bone pain soon after commencing treatment. The mechanism of action of 4-OHA in palliating patients with advanced prostatic cancer is obscure at present, but may represent an important new treatment modality which may lead to greater insight into prostatic biology.

Aged↗
PubMed1989

Polymerase chain reaction for detection of dissemination in gastric lymphoma.

The polymerase chain reaction (PCR) was used to detect malignant lymphoma cells with the bcl-2 gene rearrangement in the peritoneal washings and bone marrow of a patient with an apparently localised gastric lymphoma. After four courses of cytotoxic drug treatment the cells could no longer be detected in either site. PCR is a useful addition to the staging investigations of non-Hodgkin lymphoma and can also be used to monitor response to treatment.

B-Lymphocytes↗
PubMed1989

Experience with intermediate-dose (110-120 mg/m2) epirubicin.

A total of 23 patients with advanced malignancies received escalating doses of epirubicin (100-120 mg/m2) i.v. at 3-week intervals; 15 had received previous chemotherapy. In all, 46 courses of chemotherapy were given. Mucositis (grade II or III) occurred in 47% of courses at 120 mg/m2, but in only 15% of courses at 115 mg/m2. Myelotoxicity was manifest as leucopenia, with a median white blood count nadir of 1.9 (range, 0.8-7.0) x 10(9)/l. Nausea and vomiting were generally well controlled by prophylactic antiemetic therapy. Alopecia was WHO grade 0 in 2 patients, grade I in 1, grade II in 5 and grade III in 14. No renal or hepatic toxicity was noted, and there were no episodes of congestive cardiac failure. One fatal coronary thrombosis (proven at post-mortem examination) occurred 48 h after a dose of 115 mg/m2. Four patients developed thrombophlebitis at the injection site that was not dose-related; it occurred at doses between 100 and 120 mg/m2. Two patients who had been given chemotherapy in the past had complete responses (one penile carcinoma, one gastric carcinoma). Six patients had partial responses, including two with breast cancer, one with gastric cancer and three with sarcoma. Intermediate-dose epirubicin was well tolerated up to 120 mg/m2, when mucositis became a significant clinical problem. Preliminary data suggest promising activity in gastric cancer, breast cancer and a variety of sarcomas.

Adult↗
PubMed1989

A large outbreak of Salmonella enteritidis phage type 4 associated with eggs from overseas.

In February 1989 the largest reported outbreak to date in the United Kingdom of Salmonella enteritidis phage type 4 (PT4) infection occurred following a wedding reception at a hotel. One hundred and seventy-three people met the case definition of illness of whom 118 had the organism isolated from their stools. A further 17 were found to be S. enteritidis PT4 positive, but were asymptomatic. Lightly-cooked, egg-based sauces were the epidemiologically proven vehicles of infection. Investigations showed this outbreak to be the first to implicate imported European eggs as the source of infection. An unusual feature of this outbreak was a reported incubation period of less than 3 h for some of the confirmed cases of salmonellosis.

Animals↗
PubMed1989

Unpredictable zero drift in intravascular micromanometer tipped catheters during long term pulmonary artery pressure recording: implications for catheter design.

Zero drift may be a cause of imprecision when micromanometer tipped catheters are used for intravascular pressure measurement over long periods of time. Drift of only a few mm Hg may represent a significant error when accurate recording of low vascular pressures is required. To overcome this problem a micromanometer tipped catheter has been modified so that it can be calibrated easily while it is in the circulation. Laboratory testing has demonstrated that when zero drift occurs this intravascular "reference calibration" is a valid linear function of true zero (r = 0.999). As the sensitivity of the catheter is unaffected by zero drift, it is possible to measure pressure accurately by compensating for this zero drift. During dynamic testing of two catheters, there was a mean net drift over 24 h of -0.54 mm Hg. Clinical evaluation of the catheter was undertaken in the human pulmonary circulation in eight patients (two for 48 h, five for 24 h and one for 8 h). In contrast to the laboratory findings, over the first 4 h after catheterisation there was a phase of rapid zero drift: the net drift was -1.9 (SD 3.3) mm Hg with a range of drift of 5.5 (7.4) mm Hg. Subsequently there was gradual drift: the net drift between 4 and 24 h was -0.44 (2.1) mm Hg with a range of drift of 2.8(1.0) mm Hg; and the net drift between 24 and 48 h was 3.7(2.1) mm Hg with a range of drift of 4.1(1.9) mm Hg. During long term intravascular pressure measurement with micromanometer tipped catheters, zero drift may occur unpredictably and should be quantified.

Ambulatory Care↗
PubMed1989

Impedance changes during catheter ablation and their relationship to electrical arcing and clinical efficacy.

This study has used high energy ablative shocks in saline and in man to characterize the complex, energy dependent behavior of the impedance at the electrode-tissue interface. In vitro shocks showed a fall in impedance when an arc was formed, due to formation around the electrode of a vapor globe rendered conductive by the arc. Following arc extinction, this same vapor globe insulates the electrode, and subsequently collapses, forming a shock wave, and allowing current flow to resume. Shocks delivered to tissue specimens exhibited progressively higher impedance and less insulation as contact pressure was increased. In vivo, lesser degrees of insulation during arcing shocks were associated with greater clinical efficacy.

Animals↗
PubMed1989

Catheter ablation without fulguration: design and performance of a new system.

A new system is described for catheter ablation which comprises a short time capacitive power source and a specially designed catheter. The aim of the new system is to deliver high voltages with minimal or no arcing and thus avoid the risks associated with barotrauma. The performance of the new system was compared in a saline tank with that of the conventional system. The new system allowed significant increases in delivered voltage, current and energy without arcing. This new system should allow safer catheter ablation.

Electric Countershock↗
PubMed1989

Diurnal variation of pulmonary artery pressure in chronic heart failure.

Variation in pulmonary artery pressure has important consequences for the interpretation of isolated pressure measurements in patients with chronic heart failure. To investigate the nature of diurnal variation in pulmonary artery pressure in chronic heart failure, eight angina-free men (aged 50-72 years) with treated chronic heart failure caused by ischaemic heart disease underwent continuous ambulatory pulmonary artery pressure recording by a transducer tipped catheter. The mean (1 SD) daytime pulmonary artery pressure was 29.6 (5.0) mm Hg systolic and 13.7 (5.6) mm Hg diastolic. The mean change in pressure from day to night was +5.1 (3.2) mm Hg systolic and +3.8 (1.7) mm Hg diastolic; and the mean change from standing to lying +9.3 (2.3) mm Hg systolic and +6.4 (2.1) mm Hg diastolic. In six of the eight patients there was considerable rise in pulmonary artery pressure at night, but in the two patients with the most severe symptoms there was no nocturnal rise. In patients with chronic heart failure, nocturnal pulmonary artery pressure is not determined by postural change alone. But interpretation of isolated pulmonary artery pressure measurements must take the posture of the patient into account.

Aged↗
PubMed1989

Transvenous ablation of atrioventricular conduction with a low energy power source.

A power source modified to increase voltage delivery and minimise arcing (for a given energy) was used for transvenous ablation of atrioventricular conduction to control refractory supraventricular arrhythmias in 14 patients. Twelve had atrial fibrillation or flutter, one had atrioventricular nodal reentry tachycardia, and the other had permanent junctional reentry tachycardia. Despite treatment with 5-7 (median 6) antiarrhythmic drugs symptoms had persisted in all the patients. Cathodal discharges of 0.5-39.5 J were delivered to the distal electrode (in one case in parallel with the middle electrode). In all patients shocks produced complete atrioventricular block; this was permanent in eleven (79%). Four patients required a second procedure. In one patient, only a transient atrioventricular block could be produced and catheter ablation with a conventional power source also failed. In the other two atrioventricular conduction was modified such that previously ineffective treatment produced satisfactory control of heart rate. The cumulative energy delivered to those in whom permanent complete heart block resulted ranged from 3.6 to 97.8 (mean 38.3) J with a mean of three shocks (range 1-7) delivered per patient. During follow up of 1-28 (mean 14) months 11 patients remained in complete heart block and free of arrhythmia.

Aged↗
PubMed1989

Pulmonary infiltrates--diagnostic problems in lymphoma.

The use of invasive investigations in immunocompromised patients with pulmonary infiltrates is controversial. We report a series of 22 pulmonary lesions occurring in 19 patients with underlying Hodgkin's (7) and non-Hodgkin's (12) lymphoma in whom invasive investigations were performed. The principle techniques used were fibreoptic bronchoscopy, bronchoalveolar lavage and transbronchial lung biopsy. A specific diagnosis was made on 12 occasions (55%). Involvement of the lung with lymphoma (6) and cytotoxic drug induced pneumonitis (4) were the commonest diagnoses, infection being found on only one occasion. In 15 of these 22 procedures (68%) the information obtained made a positive contribution to patient management.

Adult↗
PubMed1989

The bcl-2 gene in primary B cell lymphoma of mucosa-associated lymphoid tissue (MALT).

The bcl-2 gene rearrangement representing t(14:18) chromosomal translocation is the most frequent karyotypic abnormality in non-Hodgkin's lymphomas of follicle center-cell lineage. By using three bcl-2 DNA probes, 21 cases of non-Hodgkin's B cell lymphoma arising from gastrointestinal mucosa and eight cases of follicular lymphomas were examined. No rearrangement of the gene could be detected in the group of gastrointestinal lymphomas, although it was identified in 75% of the follicular lymphomas. The findings suggest that these two groups of lymphomas are not a family at genetic level and support the earlier suggestion that B cell lymphomas arising from gastrointestinal mucosa-associated lymphoid tissue are not of follicle center-cell lineage.

Blotting, Southern↗
PubMed1988

Catalytic site occupancy during ATP hydrolysis by MF1-ATPase. Evidence for alternating high affinity sites during steady-state turnover.

The mechanism of ATP hydrolysis by the solubilized mitochondrial ATPase (MF1) has been studied under conditions where catalytic turnover occurs at one site, uni-site catalysis (obtained when enzyme is in excess of substrate), or at two sites, bi-site catalysis (obtained when substrate is in excess of enzyme). Pulse-chase experiments support the conclusion that the sites which participate in bi-site catalysis are the same as those which participate in uni-site catalysis. Upon addition of ATP in molar excess to MF1, label that was bound under uni-site conditions dissociates at a rate equal to the rate of bi-site catalysis. Similarly, when medium ATP is removed, label that was bound under bi-site conditions dissociates at a rate equal to the rate of uni-site catalysis. Evidence that a high affinity catalytic site equivalent to the one observed under uni-site conditions participates as an intermediate in bi-site catalysis includes the demonstration of full occupancy of a catalytically competent site during steady-state turnover at nanomolar concentrations of ATP. Improved measurements of the interaction of ADP at a high affinity catalytic site have lead to the revision of several of the rate constants that define uni-site catalysis. The rate constant for unpromoted dissociation of ADP is equal to that for Pi (4 X 10(-3) s-1). The rate of binding ADP at a high affinity chaseable site (Kd = 1 nM) is equal to the rate of binding ATP (4 X 10(6) M-1 s-1). The rate of catalysis obtained when substrate binding at one site promotes product release from an adjacent site (bi-site catalysis) is up to 100,000-fold faster than unpromoted product release (uni-site catalysis).

Adenosine Triphosphate↗
PubMed1988

Circadian variation of total ischaemic burden and its alteration with anti-anginal agents.

6264 hours of ambulatory ST segment monitoring of 150 unselected patients with proven coronary artery disease, who were off all routine anti-anginal treatments, showed 598 ischaemic episodes, of which 446 (75%) were silent (symptom-free). Most (68%) ischaemic episodes occurred between 0730 and 1930, with a peak in the morning and a lesser peak in the evening. Two subgroups were studied further in double-blind controlled trials: 33 patients had a total of 1313 hours of ST segment monitoring while treated with nifedipine; and 41 patients a total of 1581 hours while treated with atenolol. Nifedipine did not alter the circadian pattern of ischaemic episodes; atenolol abolished the morning peak, and the peak incidence of ischaemia then occurred in the evening. Circadian patterns for total duration of ischaemic episodes corresponded closely to those of episodes of ischaemia, and were similarly altered by treatment. The circadian pattern of silent ischaemic episodes and their total duration were very similar to those of total ischaemia for the group as a whole and the different subgroups. This circadian distribution of ischaemic episodes and the observed changes with treatment resemble the reported circadian variation of acute myocardial infarction and sudden death.

Adult↗