Search PubMed⌕ Search

Biomedical subjects

D Cunningham

Publications and source records attributed to D Cunningham.

At least 109 records · Page 6Linked to original sources
PubMed1993

Prognostic significance of transient ST segment changes after coronary artery bypass surgery: a long-term (4-10 year) follow up study.

OBJECTIVE: To assess the long-term (four to 10 years) prognostic significance of transient ST segment changes on ambulatory ST segment monitoring after coronary artery bypass grafting (CABG). PATIENTS AND METHODS: 76 patients (67 men, nine women) underwent CABG between 1982 and 1984 (n = 31) and between 1987 and 1988 (n = 45) and at a mean age of 57. All underwent 48 hours of ambulatory ST segment monitoring at a mean of 19 weeks after surgery. The results were available for assessment. All general practitioners were contacted and patients' notes reviewed. Patients were contacted by telephone. Details were recorded of intervening events (acute myocardial infarction, unstable angina, need for further revascularisation, and deaths). Event free survival curves were produced for those with and without transient ST segment changes during routine postoperative ambulatory ST segment monitoring. RESULTS: During 3213 hours of monitoring after CABG, 21 (27.6%) of 76 patients had transient ST segment changes, of which 70% were silent. Over a mean 70 month follow up period, patients with such ischaemic changes were no more likely to have either an objective (myocardial infarction or cardiac death) or subjective (unstable angina or another revascularisation) event than those patients without ischaemic changes. This finding was the same in patients operated on between 1987 and 1988 and between 1982 and 1984. CONCLUSIONS: Although ambulatory ST segment monitoring is becoming increasingly popular in some countries as a routine investigation for ischaemia in various coronary subgroups, the findings of such an investigation, when performed after CABG, do not help to identify a subgroup more likely to have an adverse outcome during up to 10 years of follow up. There seems to be no reason to perform this investigation after surgery, and particularly to refer patients for reinvestigation because of the detection of predominantly silent ST segment changes of uncertain relevance.

Adult↗
PubMed1993

Role of magnetic resonance imaging in predicting relapse in residual masses after treatment of lymphoma.

PURPOSE: This prospective study of patients treated at the Royal Marsden Hospital Lymphoma Unit was designed to evaluate the role of magnetic resonance imaging (MRI) in the assessment of residual masses evident on computed tomographic (CT) scanning following treatment of lymphoma. PATIENTS AND METHODS: All patients had MRI, gallium-67 single-photon emission CT (67Ga SPECT), and erythrocyte sedimentation rate (ESR) performed within 3 months of completing therapy. Patients were monitored for 1 year posttreatment and observed for signs of relapse. Investigation results were correlated with disease status, and the sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) calculated. Time-to-relapse curves were derived and the log-rank test used to determine whether patients with a positive result were more likely to have a relapse within the mass than those with a negative result. RESULTS: Thirty-four patients were studied, 14 of whom relapsed, 11 within the area of residual mass. Overall, MRI had a high specificity (90%), PPV (71%), and NPV (75%), but poor sensitivity (45%). The results for 67Ga SPECT were similar, apart from lower sensitivity (33%). ESR had inferior performance in predicting relapse compared with the other tests. MRI was the only investigation to show statistical significance (P = .14) in predicting relapse, and this was particularly evident in Hodgkin's lymphoma (P = .003). Combining results of 67Ga SPECT and MRI did not improve predictive power. CONCLUSION: These data demonstrate that MRI is a valuable tool in the setting of a residual mass after treatment, giving clinically useful prognostic information. 67Ga SPECT also has a role, but is less effective in predicting relapse than MRI.

Actuarial Analysis↗
PubMed1993

Randomised vehicle-controlled dose-finding study of glycosylated recombinant human granulocyte colony-stimulating factor after bone marrow transplantation.

A multicentre, randomised vehicle-controlled single-blind dose ranging trial of intravenous recombinant granulocyte colony-stimulating factor (rhuG-CSF) administration after BMT has been performed in 121 patients with non-myeloid malignancies. All the doses of rhuG-CSF used (2-20 micrograms/kg/day) resulted in significant acceleration of neutrophil recovery, and a dose-response effect was apparent (p < 0.05). At the 20 micrograms/kg/day dose of rhuG-CSF the median time taken to achieve a neutrophil count of > 0.5 x 10(9)/1 was reduced from 19 to 13 days (p < 0.001) and the time to achieve a neutrophil count > 1.0 x 10(9)/1 on the first of 3 consecutive days, from 26 to 14 days (p < 0.001). There was a trend to less antibiotic use in the rhuG-CSF recipients and the median time in hospital was markedly reduced by 11-15 days (p < 0.01). There was no toxicity in this study attributable to rhuG-CSF.

Adolescent↗
PubMed1993

Cardiovascular effects of chloroethylclonidine, an irreversible alpha 1B-adrenoceptor antagonist, in the unanesthetized rat: a pharmacological analysis in vivo and in vitro.

The role of vascular alpha 1B-adrenergic receptors in the regulation of arterial pressure (MAP) and heart rate (HR) was examined by assessing the effect of i.v. chloroethylclonidine (CEC; irreversible alpha 1B antagonist) in unanesthetized, normotensive Long-Evans rats. MAP, HR and the pressor response to i.v. phenylephrine (PE) were monitored for 24 hr after saline or CEC (15 mg/kg and 25 mg/kg) injection. Neither i.v. saline nor CEC affected MAP or HR throughout the course of the study, yet the PE response was maximally inhibited (> 75% at 15 min) by both doses of CEC. The PE response recovered by 2 hr at the 15-mg/kg dose but remained inhibited up to 4 hr at 25 mg/kg. At 24 hr, all cardiovascular parameters returned to control levels. CEC (100 microM, 30 min) produced irreversible blockade of norepinephrine-induced contractions in rat aortic rings; prazosin (10 nM) and sodium thiosulphate (1 mM, a reagent that inactivates aziridinium ions) reversed CEC's inhibitory effect. Precyclized CEC and its hydrolysis product beta-hydroxyethylclonidine (beta-HEC) poorly antagonized aortic alpha 1B-receptors. Ex vivo analysis of aortic rings from saline and CEC-treated rats showed that PE-induced contractions were shifted to the right and maximally depressed in a dose-dependent manner after 24 hr. These results suggest that 1) CEC produces long lasting blockade of alpha 1B-adrenoceptors in vitro and in vivo via formation of an aziridinium ion intermediate and 2) vascular alpha 1B-adrenoceptors are not coupled to the tonic physiological regulation of MAP in the rat.

Adrenergic alpha-Antagonists↗
PubMed1993

The failure of conventional methods to promote spontaneous transpyloric feeding tube passage and the safety of intragastric feeding in the critically ill ventilated patient.

Nasoenteral tube feedings are often recommended in critically ill patients when gastrointestinal tract function is intact. Conventional methods of placement include turning the patient on the right side and the use of drugs that stimulate peristalsis to promote transpyloric passage. A prospective study was initially performed to assess the success of conventional methods used to promote transpyloric feeding tube placement in patients requiring assisted ventilation admitted to the Surgical Intensive Care Unit (SICU) (Part I of the study). In 68 critically ill ventilated patients, placement of nasoduodenal feeding tubes was attempted. Successful transpyloric placement was achieved in only ten patients. There was no correlation between age, gender, admitting diagnosis, time of tube placement and successful placement. The second part of the study was initiated to assess the safety of nasogastric feeding in critically ill ventilated patients. Forty-two patients admitted to the SICU were considered candidates for gastrointestinal tract feeding and were fed through the gastric route. Twenty-five patients reached enteral feeding goal rate within 72 hours, while 34 patients achieved goal rate by five days. Eight patients required total parenteral nutrition to meet nutritional needs because of an inability to achieve adequate nutritional support enterally. There were 11 complications noted in ten patients, including one episode of aspiration pneumonia. The presence of complications was not related to age, gender, admitting diagnosis, infusion method or type of formula used. Duodenal intubation using conventional methods in critically ill ventilated patients is unsuccessful in most patients. Nasogastric feeding in this group of patients can be safely administered in selected instances.

Critical Illness↗
PubMed1992

Mutation of leucine-57 to phenylalanine in a platelet glycoprotein Ib alpha leucine tandem repeat occurring in patients with an autosomal dominant variant of Bernard-Soulier disease.

The primary sequences of the three individual glycoprotein (GP) chains, GPIb alpha, GPIb beta, and GPIX, comprising the normal platelet GPIb/IX receptor for von Willebrand factor (vWF) have recently been determined, opening the possibility for characterization of disorders of this receptor at the molecular level. The presence of a leucine tandem repeat in each of these chains is of particular interest, because such repeats may be involved in associations between polypeptide segments. We now report an autosomal dominant variant of Bernard-Soulier disease associated with the heterozygous substitution of phenylalanine for a highly conserved leucine residue within the GPIb alpha leucine tandem repeat. Affected individuals experienced a moderate bleeding tendency, thrombocytopenia, and an increased mean platelet volume. Platelet aggregation was decreased only in response to ristocetin or to asialo-vWF. The kd for 125I-vWF binding to patients platelets was significantly increased over control values at 0.5 mg/mL ristocetin, but was normal at 1.0 or 1.5 mg/mL ristocetin. While sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed an essentially normal complement of all components of the GPIb/IX complex, a minor amount of a putative proteolytic fragment was identified that migrated faster than GPIb and was immunoreactive with polyclonal anti-GPIb alpha antibody, but not with a monoclonal antibody directed against the 45-Kd amino-terminal region of GPIb alpha. However, because the great majority of patient GPIb alpha comigrates with normal GPIb alpha, the major functional abnormalities of the patient platelets are most likely a consequence of the altered structure of the nonproteolyzed protein. Full concordance within the studied family between phenotypic expression and a heterozygous single nucleotide substitution in genomic DNA coding for a phenylalanine in place of the wild-type leucine at residue 57 of the mature GPIb alpha, absence of this substitution in 266 alleles from the normal population, and the lack of any other abnormality of patient DNA throughout the entire coding sequence for GPIb alpha provide strong support that this substitution may constitute a pathologic point mutation responsible for the observed phenotypic abnormalities. While the roles that leucine tandem repeats may normally play within the GPIb/IX complex are not yet known, the perturbation of such a repeat in GPIb alpha may impair interaction with other components of the complex and/or with the binding of vWF.

Adolescent↗
PubMed1992

Gut protection by cyclophosphamide "priming" in patients receiving high-dose melphalan--effect of drug scheduling.

A "priming" injection of cyclophosphamide (400 mg/m2 given i.v. on day -7) has been shown to reduce intestinal permeability and thus gut toxicity in patients receiving high-dose melphalan. To determine the optimal timing for this injection, patients receiving 200 mg/m2 melphalan with an autologous bone marrow transplant were randomly assigned to receive cyclophosphamide at 5, 7 or 9 days before the melphalan. The median percentage of [51Cr]-ethylenediaminetetraacetic acid excretion was similar (9.1% vs 7.1% vs 7.7%, respectively), with equivalent duration of WHO grade 2-4 mucositis and diarrhoea being recorded for each group. Thus, the timing of the cyclophosphamide prime is not critical, and the priming injection may be given between 5 and 9 days prior to high-dose melphalan.

Bone Marrow Transplantation↗
PubMed1992

Expression of protease nexin-II in human dorsal root ganglia. A correlative immunocytochemical and in situ hybridization study.

Protease nexin-II (PN-II) is a potent chymotrypsin inhibitor that forms SDS-stable inhibitory complexes with epidermal growth factor binding protein, the gamma-subunit of nerve growth factor, and trypsin, and represents the secreted form of the amyloid beta-protein precursor (APP) that contains the Kunitz-type protease inhibitor domain. To determine the expression of PN-II within the peripheral nervous system, human dorsal root ganglia were processed for immunocytochemistry using well-characterized monoclonal antibodies against PN-II and for in situ hybridization studies using 35S-RNA PN-II probes for both APP751 and APP770. Highly specific immunoperoxidase staining of PN-II was demonstrated within the cytoplasm of dorsal root ganglia neurons and their processes in cryostat (fresh frozen) and vibratome (paraformaldehyde-fixed) sections. In situ hybridization using an anti-sense 35S-RNA PN-II probe demonstrated the presence of intense neuronal labeling. Labeling was not observed when the corresponding sense 35S-RNA PN-II probe was used. Although the precise functional role of PN-II/APP is not clear, the accumulation of amyloid beta-protein within the neuropil appears to be one of the earliest events in the pathogenesis of Alzheimer's disease (AD). Thus knowledge of the cell populations expressing the PN-II/APP gene would certainly be helpful for studies of the molecular mechanisms leading to the morphological and functional changes of AD. The results of this study clearly establish the expression of PN-II and its mRNA within the dorsal root ganglia neurons and their processes, and provide another point of departure for studies of the molecular mechanisms underlying the deposition of amyloid beta-protein and its relationships to the formation of neuritic plaques and neurofibrillary tangles.

Amyloid beta-Protein Precursor↗
PubMed1992

Dispersion of monophasic action potential duration: demonstrable in humans after premature ventricular extrastimulation but not in steady state.

Abnormal dispersion of repolarization may contribute to the arrhythmogenic physiologic substrate of ventricular arrhythmia. Geographic dispersion of monophasic action potential duration was determined in steady state (drive cycle lengths 600 and 430 ms) between widely spaced right ventricular endocardial sites (geographic dispersion) in 10 control patients with right ventricular disease and complicating ventricular tachycardia (n = 9), 6 patients with right and left ventricular disease and complicating ventricular tachycardia and 7 patients with ischemic heart disease and complicating ventricular tachycardia. No significant difference in geographic dispersion could be demonstrated among the groups. Difference of monophasic action potential duration at adjacent right ventricular endocardial sites (adjacent dispersion) was determined after ventricular extrastimulation during construction of simultaneous electrical restitution curves in the same patient groups. Maximal adjacent dispersion over the electrical restitution curve was compared between disease and control groups. There was a significant difference in observations of maximal adjacent dispersion in patients with right ventricular disease and complicating ventricular tachycardia (range 5 to 85 ms, median 22.5; 14 pairs of sites; p less than 0.05) and patients with right and left ventricular disease and complicating ventricular tachycardia (range 5 to 50 ms, median 17.5; 14 pairs of sites; p less than 0.05) compared with control patients (range 5 to 20 ms, median 10; 15 pairs of sites). This difference was not evident when patients with ischemic heart disease and complicating ventricular tachycardia (range 5 to 25 ms, median 12.5; 12 pairs of sites) were compared with control patients. Maximal percent monophasic action potential shortening from steady state was significantly greater (p less than 0.001) in both groups with greater adjacent dispersions, and prolongation of activation time at monophasic action potential recording sites after premature extrastimulation tended to be greater in patients with right or right and left ventricular disease and complicating ventricular tachycardia. It is concluded that in disease, exaggeration of monophasic action potential shortening after premature ventricular extrastimulation may contribute to the electrophysiologic arrhythmogenic substrate.

Action Potentials↗
PubMed1992

Intra-abdominal panniculitis can mimic recurrent stomach carcinoma.

Carcinoma of the stomach is increasingly treated with chemotherapy. We describe two cases of intra-abdominal panniculitis in patients after laparotomy and chemotherapy for stomach carcinoma. Intra-abdominal panniculitis can result in mass lesions in the mesentery and omentum. The diagnosis should be considered in patients who have undergone chemotherapy for stomach carcinoma and who develop abdominal masses.

Abdomen↗
PubMed1992

Efficacy of twice daily versus three times daily oral ondansetron in the prevention of chemotherapy induced emesis: a randomized, single-blind, multicentre study. The Ondansetron International Emesis Study Group.

Following a single intravenous dose given pre-chemotherapy, the efficacy and tolerability of oral ondansetron treatment given twice daily was compared with the established three times daily oral supplementary regimen in the prophylaxis of nausea and vomiting induced by cyclophosphamide (greater than or equal to 500 mg/m2) in combination with doxorubicin (greater than or equal to 40 mg/m2) or epirubicin (greater than or equal to 40 mg/m2). Oral ondansetron given twice daily or three times daily was equally effective in controlling nausea and emesis. The twice daily oral treatment prevented emesis in 73% of patients in the first 24 hours and in 65% of patients over 3 days. Both dose schedules were safe and were tolerated well. Twice daily oral ondansetron showed good efficacy for controlling emesis and nausea in oncology outpatients.

Administration, Oral↗
PubMed1992

Electrical restitution in the endocardium of the intact human right ventricle.

OBJECTIVE: To characterise electrical restitution in the intact human heart. PATIENTS AND METHODS: A series of monophasic action potential electrical restitution curves were constructed from a single right ventricular endocardial site in eight patients (three men) without structural heart disease aged 52-68 (mean 55 years). A combination pacing/monophasic action potential electrode was used to pace and record monophasic action potentials at drive cycle lengths of from 350 ms to 1500 ms. Ventricular extrastimuli were delivered at 20 cycle intervals and decreased from the longest coupling interval attainable without escape beats. RESULTS: Restitution curves shifted downward and towards the left; steady state action potential duration shifted from the restitution plateau and descended the curve, the amount of shift being linearly related to drive cycle length in two patients in whom the relation could be assessed; the amount of monophasic action potential shortening was a function of the degree of prematurity and that relation was unaffected by drive rate; the magnitude of restitution and the time constant of the restitution curve were not changed significantly by altered drive cycle length. CONCLUSION: In the intact heart in vivo, electrical restitution (of the monophasic action potential) has similar characteristics to those (of the transmembrane action potential) in cellular preparations in vitro. Thus the alteration of action potential plateau currents by instantaneous rate change or drug effects, which can be directly observed by techniques available to the cellular electrophysiologist, may be indirectly assessed in vivo by characterisation of the effect of these on electrical restitution.

Action Potentials↗
PubMed1992

Impact of catheter and surgical ablation on arrhythmia treatment in a tertiary referral centre.

Invasive cardiac electrophysiology studies began as diagnostic studies. The past decade has seen the introduction of several new treatments which have broadened the scope of invasive electrophysiology studies. In particular, the development of catheter ablation techniques increasingly allows curative treatment to be delivered in the catheter laboratory. The workload of electrophysiological procedures has steadily increased in our tertiary referral centre. Over 1000 patients have been treated in the past 20 years and it is projected that 219 new patients will be treated in 1991 and 342 procedures will be carried out. Over 25% of patients now receive either catheter or surgical ablation and almost 80% of these are cured permanently without the need for further drug treatment. The development of safer techniques for catheter ablation has led to its increased use and a decline in surgical ablations. Because catheter ablation is a much simpler and less traumatic procedure than surgical ablation there are great advantages both for the patient and in terms of cost-effectiveness. Antitachycardia pacing, relatively common in 1985, has now largely been supplanted by ablation and implantation of defibrillators. As the tendency to non-pharmacological treatment increases and evidence mounts that cost-effectiveness is greater for electrophysiological treatments, the implications for the funding of electrophysiology services grow. The initially high cost of curative treatment needs to be balanced against the longer term and potentially higher costs of palliative drug treatment. The potential to cure patients with catheter procedures may lead to a greater demand for this expertise and a need for an increase in training and facilities.

Arrhythmias, Cardiac↗
PubMed1992

Multiple myeloma: appearance at MR imaging.

Magnetic resonance (MR) imaging examinations of the lumbar spine and clinical and laboratory findings in 32 patients with multiple myeloma were reviewed. On T1-weighted images, signal intensity (SI) of the vertebrae approximated that of muscle in 14 cases and was intermediate (between the SIs of muscle and fat) in 18. Definite foci of decreased SI were seen in eight cases (25%), and foci of increased SI, representing fatty infiltration, were seen in 12 (38%). On T2-weighted images, SI approximated that of muscle in 17 cases and was intermediate in 15. Definite foci of increased SI were seen in 17 (53%). Of 38 vertebral compression fractures (including 18 in nine additional patients), foci of abnormal SI consistent with tumor on either T1- or T2-weighted images were seen in 19 cases (50%). There was no correlation between MR imaging findings and laboratory or bone marrow findings. Foci of presumed tumor were better or exclusively shown on T2-weighted images in 11 of 17 patients (65%) with identifiable focal disease. Other suggestions of multiple myeloma on T1-weighted images may be the absence of fatty replacement or a generalized decrease in SI.

Female↗
PubMed1992

High-dose busulfan in patients with myeloma.

PURPOSE: To evaluate the use of high-dose busulfan (HDB) with autologous bone marrow transplantation (ABMT) in patients with myeloma. PATIENTS AND METHODS: Fifteen patients received HDB (16 mg/kg), eight of whom received high-dose melphalan (HDM) but had experienced a short remission or progression-free interval. Two patients had received HDM on two previous occasions, one had no response to low-dose melphalan, and four had impaired renal function (edathamil clearance < 40 mL/min). All patients received induction chemotherapy before HDB. RESULTS: Two patients were in complete remission (CR) after induction chemotherapy before HDB. Of the remaining 13 patients, four (31%) achieved CR and two (15%) achieved a partial remission for an overall response rate of 46%. There were three treatment-related deaths, but the toxicity was otherwise predictable and manageable. CONCLUSIONS: In heavily pretreated patients, HDB results in a relatively high response rate. It can also be used safely in patients with renal impairment who are not suitable for HDM.

Adult↗
PubMed1992

Results of a double blind placebo controlled study of ondansetron as an antiemetic during total body irradiation in patients undergoing bone marrow transplantation.

Total body irradiation (TBI) is a highly emetogenic component of the majority of conditioning regimens in use for bone marrow transplantation. Conventional antiemetic therapy fails to control nausea and vomiting induced by single fraction TBI in as many as 50% of patients. In a double blind study of 20 patients undergoing marrow transplantation, a single 8 mg ondansetron dose was compared with placebo given immediately prior to TBI. Our routine premedication of phenobarbitone and corticosteroid was also administered to all patients. All patients had received high dose melphalan the previous evening. Only 1 of the 10 patients in the ondansetron group experienced an emetic event compared with 5 of the 10 in the comparison group (p = 0.029). No significant adverse events were observed. Ondansetron appears to have extremely useful antiemetic activity during single fraction low dose rate TBI.

Adult↗