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Biomedical subjects

D Cunningham

Publications and source records attributed to D Cunningham.

At least 253 records · Page 14Linked to original sources
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↗
PubMed1988

Pyridoxal 5'-diphospho-5'-adenosine binds at a single site on isolated alpha-subunit from Escherichia coli F1-ATPase and specifically reacts with lysine 201.

Pyridoxal 5'-diphospho-5'-adenosine (PLP-AMP), an adenine nucleotide affinity analog, was found to bind in a saturable fashion to isolated alpha-subunit from Escherichia coli F1-ATPase with a stoichiometry of one mol/mol and a Kd approximately 150 microM. The binding was shown to be specific by the following criteria: 1) ATP reduced the binding of PLP-AMP by 80%, and 2) PLP-AMP, like ATP, induced a conformational change which increased the mobility of alpha-subunit in nondenaturing polyacrylamide gel electrophoresis and rendered alpha-subunit resistant to mild trypsin proteolysis. A stable adduct was formed between isolated alpha-subunit and [3H] PLP-AMP after reduction with NaBH4. alpha-Subunit labeled to the extent of 0.4-0.7 mol/mol was digested with trypsin and subjected to high pressure liquid chromatography purification, yielding a single labeled peptide. Automated amino acid sequencing showed that residue alpha-Lys-201 was specifically labeled. The results suggest that Lys-201 occupies a position proximate to the phosphate groups of bound ATP in the alpha.ATP complex. PLP-AMP did not support repolymerization of isolated alpha-, beta-, and gamma-subunits, consistent with previous reports that subunit repolymerization in vitro is dependent upon the presence of nucleoside triphosphate. Further, PLP-AMP-labeled alpha-subunit could not be reconstituted with isolated beta- and gamma-subunits in the presence of ATP, showing that occupation of the alpha-subunit nucleotide site by PLP-AMP impairs normal subunit-subunit interaction.

Adenosine Diphosphate↗
PubMed1988

The pharmacokinetics of high dose cyclophosphamide and high dose etoposide.

We have studied the pharmacokinetics of single agent high dose cyclophosphamide (HDC) (160-240 mg kg-1) given as repeated intravenous (i.v.) infusions to six patients with small cell lung cancer (SCLC), and HDC (180 mg kg-1) combined with etoposide (750-1000 mg m-2) as repeated i.v. infusions to five patients with SCLC and two patients with teratoma. HDC has a similar pharmacokinetic profile to low dose cyclophosphamide, with a half-life of 4.83 +/- 1.3 h. Repeated administration of HDC produced a small but significant shortening of the half life (P = 0.02). The terminal half-life of high dose etoposide was 7.7 +/- 2 h which is similar to our previous results with low dose etoposide (50-300 mg m-2), but the volume of distribution which was 35.5 +/- 11.6 1. was significantly increased (P less than 0.001). Plasma steady state concentrations of 26.2 +/- 11.7 micrograms ml-1 were achieved. The possible mechanism for the alteration of volume of distribution of etoposide will be discussed.

Carcinoma, Small Cell↗
PubMed1988

A randomized trial of oral nabilone and prochlorperazine compared to intravenous metoclopramide and dexamethasone in the treatment of nausea and vomiting induced by chemotherapy regimens containing cisplatin or cisplatin analogues.

Eighty patients receiving their first course of chemotherapy with regimens containing cisplatin or cisplatin analogues entered this open crossover study comparing nabilone 2 mg and prochlorperazine 5 mg given orally every 12 h for four doses against metoclopramide 2 mg/kg loading dose intravenously (i.v.), then 3 mg/kg as an (i.v.) infusion over 8 h and dexamethasone 20 mg (i.v.) over 3-5 min at the time of chemotherapy. There was complete control of nausea and vomiting in 24 patients (32%) given metoclopramide and dexamethasone compared to 14 patients (19%) given nabilone and prochlorperazine. For the 70 patients who completed the crossover assessment of emesis on a linear analogue scale significantly favoured metoclopramide and dexamethasone (P = 0.02). However, there was no overall patient preference for the metoclopramide and dexamethasone combination (nabilone and prochlorperazine 31 vs. metoclopramide and dexamethasone 26; 13 no preference), because a significant proportion of the patients receiving the cisplatin analogue carboplatin preferred nabilone and prochlorperazine (16 vs. 5; 1 no preference; P = 0.013). For patients receiving cisplatin chemotherapy metoclopramide and dexamethasone remains the antiemetic of choice but for regimens containing carboplatin, nabilone and prochlorperazine is better tolerated and preferred by the patients.

Adolescent↗
PubMed1988

Basal lamina of rat myocardium. Its fate after death of cardiac myocytes.

As part of a study of the interactions between myocardial cells and extracellular matrix during healing of necrotic lesions, we have examined the fate of myocyte basal lamina (BL) after injury with ischemia, freeze-thawing, or isoproterenol. Using light and electron microscopy, and antibodies to three BL-associated antigens, we found that the BL of necrotic myocytes remained largely intact and continued to delineate the myocyte compartment from connective tissue space. Inflammatory cells entered the myocyte compartment through holes in the acellular BL and removed cell debris. The holes may have been produced by inflammatory cells and/or by the stretching force of the beating heart. After removal of debris, some BL sheaths of necrotic myocytes collapsed, resulting in spatial approximation of vessels. Interstitial cells deposited collagen and elastic fibers in the connective tissue space and within portions of the myocyte compartment. The acellular myocyte BL, collapsed or not, retained normal antigen staining for type IV collagen, laminin, and heparan sulfate for about 10 days, then showed diminished staining in patchy areas. These areas may correspond to BL disruption and degradation in conjunction with fibrosis, although a substantial amount of acellular BL remained in situ and became embedded in scar tissue. At least two types of granulo-vesicular bodies, measuring 25 to 60 and 60 to 160 nm respectively, were associated with the acellular BL; these were of unknown origin and function. The study shows that the fate of acellular BL in injured myocardium is similar to the fate of BL in other injured tissues; however, the appearance of holes in acellular BL, within hours after injury, is unusual and may enhance scar tissue formation. Whether the acellular BL contributes to regeneration of myocardium, as do acellular BLs in other injured tissues, remains to be determined.

Animals↗
PubMed1988

Myocyte reactions at the borders of injured and healing rat myocardium.

To better understand the apparent tendency of myocardium to heal by scarring rather than by restoration of normal structure, we have examined by light and electron microscopy the basic reactions of rat ventricular myocytes and their interactions with the extracellular matrix. Using three different types of necrotizing injuries, we found that necrotic myocytes separated from viable myocytes at intercalated discs leaving blunt-ended stumps at the edge of each lesion; the basal lamina of necrotic myocytes remained largely intact and spanned the gap between viable myocytes on opposite sides of each lesion. A small number of stumps were capped off by a new layer of basal lamina and showed no evidence of proliferative activity. The majority of the stumps developed cell processes that extended along the acellular myocyte basal lamina sheaths. These processes had one of two different fates. Some became apposed to similar processes, formed intercalated disc attachments, increased myofibrillar mass, and appeared to be associated with muscle reconstruction. Others developed elongate tapered ends, which terminated in myotendinous connections to scar tissue. The outcome of healing necrotic myocardium, like the healing of noncardiac necrotic tissue injuries, appears to be a function of cell growth and extracellular framework guidance; however, unlike healing of noncardiac tissues, healing of myocardium is uniquely complicated by continuing muscle contractions. We think the rhythmic pulling at the edges of necrotic lesions induces formation of myotendinous attachments, which anchor myocytes to scar tissue and probably prevent further growth.

Animals↗