Biomedical subjects

K Fox

Publications and source records attributed to K Fox.

At least 217 records · Page 12Linked to original sources

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

Evidence for a specific role for cortical NMDA receptors in slow-wave sleep.

Iontophoresis of the N-methyl-D-aspartic acid (NMDA) receptor antagonist 2-amino-5-phosphonovaleric acid (2-APV) was found to suppress spontaneous bursting activity of layer V cortical neurones during stage 3/4 sleep in unrestrained, normally behaving rats. Iontophoresis of NMDA, on the other hand, increased cortical burst durations and increased the number of spikes per burst. 2-APV was found not to alter cells' responses to tactile stimulation or the generation of neuronal spindling activity during stage 2 sleep. These results provide the first evidence that NMDA receptors subserve a specific function in the neocortex of the behaving animal, by gene-rating burst activity in cortical neurones during stage 3/4 of the natural sleep state. The activation of NMDA/2-APV-sensitive cortical receptors by afferents from the anterior intralaminar nuclei in the generation of bursts by cortical cells during stage 3/4 sleep is discussed.

2-Amino-5-phosphonovalerate↗

PubMed1988

Cardiac transplantation in severely ill patients requiring intensive support in hospital.

Sixty four patients were referred for cardiac transplantation from a single cardiac team at this hospital between October 1984 and December 1986. Of these patients, 33 were referred for urgent transplantation, all of whom required intensive treatment in hospital with intravenous infusions of cardiac drugs, intra-aortic balloon counterpulsation, peritoneal dialysis, ventilation, or any combination of these to sustain life. Of these 33 patients, six died while awaiting transplantation, one was removed from the waiting list for a transplant, and 26 received cardiac transplants. There were five deaths within 24 hours of operation and one death 10 days after the operation. Twenty of those who had surgery had a successful outcome of transplantation, but there was one late death 10 weeks postoperatively and a further death 31 months after surgery. Eighteen patients were alive and well 10 to 33 months (mean 19.4 months) after transplantation, with an overall survival rate after surgery of 69%. Provided that surgery can be performed before renal failure has progressed such that renal dialysis [corrected] is necessary, the results are excellent (surgical survival 85.5%) and, we believe, justify the expenditure and staffing requirements necessary to treat these terminally ill patients.

Adolescent↗

PubMed1988

Labetalol in normotensive patients with angina pectoris.

Labetalol, an alpha-beta-blocker, has been shown to have vasodilating as well as beta-blocking properties. From the theoretical point of view such a drug is likely to be beneficial in the treatment of angina pectoris. There are very few studies investigating the effects of labetalol in normotensive patients with angina pectoris. The three major controlled trials that have been published show that labetalol reduces angina frequency and prolongs exercise duration. In one study the effects of labetalol in anginal subjects using ambulatory monitoring was performed and showed a reduction in silent ischemia as well as a reduction in angina pectoris. Thus labetalol would appear to be an effective antianginal agent. Further studies are necessary to determine if the anti-anginal effect is entirely due to the beta-receptor-blocking activity of the drug or whether labetalol's vasodilating property has important additional benefit.

Angina Pectoris↗

PubMed1988

Massive haemoptysis in the acquired immunodeficiency syndrome.

A 32-year-old male intravenous drug abuser was admitted to our institution with constitutional symptoms and sputum smears containing acid-fast bacilli, but no parenchymal disease on chest radiograph. He subsequently developed massive haemoptysis and required an emergency lobectomy. The pathology specimen revealed miliary tuberculosis with extensive caseation, schistosomiasis and cytomegalovirus. This is the first report of massive haemoptysis in the acquired immunodeficiency syndrome. The severe pulmonary haemorrhage was most likely due to miliary tuberculosis.

Acquired Immunodeficiency Syndrome↗

PubMed1988

Labetalol in the treatment of stable exertional angina pectoris: a comparison with nifedipine.

Labetalol, a combined alpha- and beta-receptor antagonist, was compared with nifedipine in a placebo-controlled, randomized double-blind cross over study (four week treatment periods) of 11 normotensive patients with stable exertional angina pectoris. Standard recommended doses of both drugs (labetalol 200-400 mg twice daily, nifedipine 10-20 mg three times daily) were used. Angina frequency was similar during the placebo washout period and treatment with the two drugs. The duration of treadmill exercise to angina, ischaemia (greater than 1 mm ST segment depression), and end of exercise was increased by both labetalol and nifedipine when compared with placebo, but there was no difference between the two drugs. Ambulatory ST segment monitoring demonstrated that the frequency, duration and magnitude of ST segment depression, whether painful or silent, were unaffected by either drug. Labetalol is an effective agent in improving exercise tolerance in normotensive patients with stable exertional angina pectoris, with an efficacy similar to that of nifedipine.

Adult↗

PubMed1988

Silent myocardial ischaemia in chronic stable angina: a study of its frequency and characteristics in 150 patients.

One hundred and fifty unselected patients with documented coronary artery disease were studied to establish the frequency and characteristics of silent myocardial ischaemia. Patients underwent ambulatory ST segment monitoring off all routine antianginal treatment (total 6264 hours) and exercise testing (n = 146). Ninety one patients (61%) had a total of 598 episodes of significant ST segment change, of which 446 (75%) were asymptomatic. Twenty seven patients (18%) had only painless episodes; 14 (9%) patients only painful episodes; 50 patients (33%) had both painless and painful episodes. The mean number of ST segment changes per day was 2.58 (1.95 silent); however, 11 patients (7%) had 50% of all silent episodes, and 48 patients (32%) had 91% of all silent episodes. Fifty nine patients (39%) had no ST segment changes on ambulatory monitoring, and 73 patients (49%) had no evidence of silent ischaemia. Episodes of silent ischaemia occurred with a similar circadian distribution to that of painful ischaemia, predominantly between 0730 and 1930. There was a similar mean rise in heart rate at the onset of both silent and painful episodes of ischaemia. Silent ischaemia was significantly more frequent in patients with three vessel disease than in those with single vessel disease, and was also significantly related to both time to 1 mm ST depression and maximal exercise duration on exercise testing. There was a highly significant relation between the mean number and duration of episodes of silent ischaemia in patients with positive exercise tests when compared with those with negative tests. No episode of ventricular tachycardia was recorded in association with silent ischaemic change.

Adult↗

PubMed1988

Lack of effect of warfarin on the restenosis rate or on clinical outcome after balloon coronary angioplasty.

Between September 1985 and April 1987, 110 consecutive patients who had successful coronary angioplasty were included in a randomised prospective controlled evaluation of the effects of warfarin on restenosis. The warfarin (n = 56) and the control (n = 54) groups were not different in terms of age, sex, previous coronary bypass surgery or coronary balloon angioplasty, severity of symptoms, and frequency of multivessel disease or of total coronary occlusions. Warfarin was started on the day of the procedure and the dosage was adjusted to maintain the thromboplastin international normalised ratio greater than or equal to 2.5. One hundred and five (96%) of the patients were given verapamil and other antianginal drugs were prescribed as needed. Low molecular weight dextran and heparin were given during the procedure and heparin was continued for 24 hours in all patients. One hundred and eight (98%) of patients were followed up clinically after a median of five months (range 1-20). Eighty five (77%) had follow up angiography at five months. In the warfarin group symptoms improved in 46 (85%) patients by at least 1 angina class and 31 (57%) were symptom free; the exercise test remained positive in 20 (36%) patients and the angiographic restenosis rate was 25% per lesion and 29% per patient. There were no major bleeding complications. In the control group 46 (85%) patients were improved by at least 1 angina class and 31 (57%) were symptom free; the exercise test was positive in 11 (21%) patients and the angiographic restenosis rate was 33% per lesion and 37% per patient. Although the incidence of angiographic restenosis tended to be lower with warfarin, none of these differences was significant. These data suggest that the combination of verapamil and warfarin, in the absence of aspirin, is not significantly better than verapamil alone in preventing symptom recurrence or angiographic restenosis after coronary angioplasty.

Adult↗

PubMed1987

Spatiotemporal convergence and divergence in the rat S1 "barrel" cortex.

The size and response magnitude of receptive fields were evaluated for cells in the rat cortical barrel-field by using standard vibrissal deflections of 1.14 degrees. Such stimuli fell within the plateau region of stimulus-response curves. The response of all neurones to all vibrissae within and surrounding centre-receptive fields were analysed for probability and latency of response. It was found that cells in supragranular layers had small centre-receptive fields (average 1.6 vibrissae) with small excitatory surrounds (1.5 vibrissae) while cells in the granular layers had small, powerful centre-receptive fields (1.4) with moderately large excitatory surrounds (2.6). Neurones in infragranular layers possessed large but weak centre-receptive fields (2.6) with large surrounds (3.5). Sixty-four neurones in layer IV were studied, the precise locations of which were identified by using dye lesioning and cytochrome oxidase staining. There were no differences in receptive field size for cells within septa and barrel hollows, but the latter were twice as likely to produce two or more spikes per stimulus from the principal vibrissa (65% against 33%). Histological analysis showed that the principal vibrissa was synonymous with the appropriate vibrissa for the barrel on 86% (55 of 64) of occasions. A quantitative analysis of convergent input to three neighbouring barrels (E1, E2, and D1) showed considerable graded overlap of receptive field surrounds, although facial hair adjacent to the mystacial pad only influenced cells on the edge of the barrel-field. Individual vibrissae exhibited significant divergent input to adjacent inappropriate barrels, being preferentially directed to distant septal rather than barrel hollow cells. An analysis of latencies showed that 40% of barrel hollow cells and 48% of barrel septal cells responded at short (less than 10 ms) latencies to their appropriate vibrissa. In contrast, responses to inappropriate vibrissae were overwhelmingly of long latency (10-greater than 30 ms), only 2% of inappropriate responses from barrel hollow cells and 13% from septal cells being of short latency. These results suggest that direct inputs largely project to appropriate barrels. The possibility that divergent inputs are generated by intracortical mechanisms is discussed.

Animals↗

PubMed1987

The role of ambulatory ST-segment monitoring in the diagnosis of coronary artery disease: comparison with exercise testing and thallium scintigraphy.

The value of ambulatory ST-segment monitoring in the detection of underlying coronary artery disease was investigated in one hundred consecutive patients who underwent exercise testing and coronary arteriography for chest pain. Forty-seven also had thallium-201 radioisotope imaging performed. Six of the 26 patients with normal coronary arteries and 52 of the 74 patients with significant coronary artery disease had ST-segment changes during 48 h of ambulatory monitoring (sensitivity 77%). In comparison, the sensitivity of conventional exercise testing was 73% and specificity was 81%. Previous myocardial infarction did not influence the results, but patients with poor left ventricular function more often had absence of ambulatory ST-segment changes. Three-vessel coronary artery disease was detected more efficiently (sensitivity 80%), compared with single vessel disease (sensitivity 50%). Thallium scintigraphy demonstrated defects of uptake in nine patients without ambulatory ST-segment changes (sensitivity 82%, specificity 71%). The majority of these patients had small inferior or posterior defects in thallium uptake. Only one patient with ambulatory ST-segment changes had normal coronary arteries and demonstrable spasm. Thus, ambulatory ST-segment monitoring is as valuable as stress testing in the detection of coronary artery disease and in addition helps detect patients with coronary spasm and normal coronary arteries.

Ambulatory Care↗

PubMed1987

The pathology of the early and late stages of primary pulmonary hypertension.

During the course of a case of primary pulmonary hypertension occurring in a 24 year old man lung tissue became available at heart-lung transplantation in 1986 and from a lung biopsy carried out in 1981. In 1986 the sections showed classic plexogenic pulmonary arteriopathy. In 1981 they revealed migration of myofibroblasts into the intima and lumen of pulmonary arteries and arterioles, the identification of the cells being confirmed by electron microscopy. During the five years that the pulmonary vascular pathology progressed to the formation of plexiform lesions there was an increase in the number of bronchiolar endocrine cells that were immunoreactive to bombesin and calcitonin. This study demonstrates that the classic pathogenesis of primary plexogenic pulmonary arteriopathy originates years earlier as a migration of cells of muscular pedigree from the media into the intima of the pulmonary arteries and arterioles.

Adult↗

PubMed1987

Coronary balloon angioplasty for elderly patients with severe angina.

From February 1983 to December 1986, 65 angioplasty procedures were attempted in 51 patients aged 65 or more. All had angina refractory to medical treatment and 89% of procedures were performed in patients in Canadian Cardiovascular Society angina class III or IV. Sixty eight per cent of patients had multivessel disease. Angioplasty was attempted on a single vessel in 52 instances (80%) and on multiple vessels in 13 (20%). The initial success rate was 75% for stenosis and 44% for occlusion. No attempt was made to treat all visible lesions in every case. At least one major complication occurred in 6.2% of the procedures: Q wave infarction in 4.6%, emergency surgery in 4.6%, and death in 4.6%. After a median follow up of four months (range 1-31) 37% of the patients in whom the procedure was initially successful were asymptomatic and 76% were improved by at least one Canadian Cardiovascular Society angina class. Angiographic restenosis occurred in 28% of treated lesions and 39% of patients had at least one recurrent stenosis. Among the patients with an initially successful procedure, 11% needed surgical revascularisation during the follow up period compared with 50% of those with a failed angioplasty. Balloon coronary angioplasty can be an effective form of treatment for the relief of severe angina in elderly patients.

Aged↗

PubMed1987

WR-2721 and high-dose cisplatin: an active combination in the treatment of metastatic melanoma.

Cisplatin, alone or in combination with other chemotherapeutic agents, is relatively inactive against metastatic melanoma. Prior trials have demonstrated partial response (PR) rates of less than 10% with cisplatin alone. WR-2721 is an organic thiophosphate compound, which in the animal model, selectively protects normal tissues against the toxicity of cisplatin chemotherapy. During the course of a phase I trial of WR-2721 and cisplatin, objective PRs were noted in patients with far advanced metastatic melanoma. These observations led us to perform a phase II trial of WR-2721 and cisplatin. Thirty-six patients received 128 courses of WR-2721 before cisplatin (60 to 150 mg/m2). All patients had progressive disease before treatment. Objective PRs were observed in 19 of 36 evaluable patients (53%). Three additional patients had minor responses (MRs). PRs occurred in 53% of patients with prior chemotherapy (ten of 19). Sites of responding metastases were subcutaneous disease (15 of 19 patients), lymph nodes (16 of 21 patients), lung (four of ten patients), and liver (eight of 17 patients). The median duration of response was 4 months, with a mean of 4.5 months (range, 1 to 8 months). Transient nephrotoxicity was observed in less than 5% of courses. In all cases, renal function returned to normal within 1 to 2 weeks. Hematologic toxicity was mild and infrequent. Nine patients developed peripheral neuropathy following a median cisplatin dose of 670 mg/m2. Twenty patients experienced mild clinical hearing loss. These data suggest that WR-2721 may potentiate the antitumor activity of cisplatin in metastatic melanoma.

Adult↗

PubMed1986

The role of the anterior intralaminar nuclei and N-methyl D-aspartate receptors in the generation of spontaneous bursts in rat neocortical neurones.

The nature of spontaneous unitary activity of rat neocortex was investigated during slow wave sleep and urethane anaesthesia. Neurones in layer IV and V locations fired in a burst-pause pattern at a low burst repetition rate (0.5-4 per second) during both stage 3/4 sleep and urethane anaesthesia. Occasionally an alternative mode of firing (spindle clusters), associated with focal spindle wave activity, was also found to occur in both states. Using dual microelectrode implants it was found that the onset times of bursts (but not spindle clusters), coincided in the same and opposing cortices, whether in functionally similar or disparate areas. The highest probability was that burst onsets occurred simultaneously (resolution = 2.56 ms, interquartile range = 40 ms). Spontaneous unitary activity was investigated in the thalamus for temporal correlation with spontaneous unitary activity in neocortex under urethane anaesthesia. Neurones of the anterior intralaminar group (aIL) consistently fired in a burst-pause pattern such that each aIL burst showed a strong tendency to precede a cortical burst. Unilateral electrical stimulation of the aIL nuclei evoked widespread bilateral entrainment of cortical bursts. In contrast stimulation of VPl, or cutaneous sites, evoked only short duration spike responses together with burst abolition in the appropriate restricted Sml area. Ionophoresis of NMDA (N-Methyl D-Aspartate) onto Sm1 neurones increased the probability of cortical burst responses to aIL stimulation in addition to decreasing the latency by 20-40 ms (n = 11). Ionophoresis of 2APV (2-amino 5-phosphono valeric acid) caused simultaneous abolition of spontaneous cortical bursts and bursts evoked by aIL stimulation. Short latency responses to cutaneous and VPl stimulation were unaffected by ionophoresis of 2APV sufficient to cause burst elimination, suggesting that this pathway does not operate via a 2APV sensitive receptor mechanism. Anatomical features of the aIL nuclei and their overall cortical projection pattern are discussed in relationship to these findings. The activation of cortical NMDA/APV sensitive receptors by aIL afferents in the "spontaneous" generation of bursts in cortical cells is discussed.

Action Potentials↗

PubMed1986

Phase I/II trials of WR-2721 and cis-platinum.

Renal dysfunction is a well-known dose-limiting toxicity of cis-platinum. Previous studies demonstrated a 32% incidence of nephrotoxicity following a 100 mg/M2 single dose of cis-platinum with mannitol diuresis. WR-2721 is an aminothiol which in the animal model improves renal tolerance to cis-platinum by factors of 1.3 to 1.7. Phase I trials were initiated to establish the toxicity when WR-2721 was given prior to escalating doses of cis-platinum. Fifty-two patients received 161 courses of WR-2721 prior to cis-platinum (60-150 mg/M2) with mannitol and hydration. Nephrotoxicity, measured by twice weekly serum creatinines and monthly creatinine clearances, occurred in only 10/97 (10%) courses with 120 mg/M2 of cis-platinum. No patient experienced a creatinine elevation after 135 mg/M2 of cis-platinum. With 150 mg/M2 of cis-platinum, 6/17 (35%) courses were associated with transient nephrotoxicity. Five patients who developed transient creatinine elevations following 150 gm/M2 of cis-platinum were subsequently retreated with WR-2721 and cis-platinum (100 mg/M2) without nephrotoxicity. Bone marrow suppression was mild and infrequent. Mild to moderate peripheral neuropathies were noted in seven patients following cumulative cis-platinum doses ranging from 460-1160 mg/M2. Objective partial responses were observed in 26/45 (58%) patients with measurable or evaluable disease. Thus, there is no evidence that WR-2721 protects against the antitumor efficacy of cis-platinum in man. Compared to retrospective series, our data suggest that WR-2721 may provide some protection against platinum-induced nephrotoxicity and neurotoxicity. Controlled trials will be required to define the potential clinical benefit of WR-2721 and cis-platinum.

Amifostine↗

PubMed1986

[Single photon emission computed tomography of patients with benign and malignant spinal diseases].

SPECT has been used in a comparative study with planar bone scintigraphy in 54 patients. Spatial resolution of the method is sufficient to localise the vertebral bodies, the spinous processes, the intervertebral, costotransverse and costovertebral joints. In all patients it was possible to relate the areas of increased uptake to specific anatomical sites of the spine known to be affected in the different conditions. A detailed localisation is rarely possible using planar scintigraphy alone, due to the complex osseous anatomy of the spine. In some patients lesions could be seen only with SPECT. SPECT is an invaluable supplement to planar scintigraphy of the spine.

Adult↗

PubMed1985

Dimensional accuracy of magnetic resonance in studies of the heart.

Magnetic resonance (MR) can provide high-resolution tomographic images of the heart at any part of the cardiac cycle. Tests on static and dynamic phantoms showed that the technique can give accurate measurements of ventricular wall thickness, cavity volume, and stroke volume. In 20 patients with angina pectoris, electrocardiographically gated MR images of the left ventricle were compared with X-ray contrast ventriculograms. There was good correlation with the anteroposterior ventriculogram, but poorer correlation in the lateral projection because of difficulty in locating the aortic valve precisely on the ventriculogram. In 20 normal subjects, left and right ventricular volumes at end-diastole and end-systole were measured by summing the areas of the cavities in multiple contiguous sections. Stroke volumes and ejection fractions were thus calculated, and the ratio of left to right ventricular stroke volume was very close to the theoretical value of 1, in all cases. In any individual volume measurement, the error was approximately 2%. MR therefore provides an accurate non-invasive method of studying cardiac dimensions and function.

Animals↗

PubMed1985

Chemoattractant-elicited alterations of cAMP levels in human polymorphonuclear leukocytes require a Ca2+-dependent mechanism which is independent of transmembrane activation of adenylate cyclase.

The affinity of the chemoattractant receptor for N-formyl-methionyl-leucyl-phenylalanine (fMet-Leu-Phe) on human polymorphonuclear leukocytes (PMNs) is regulated by guanine nucleotides, and chemoattractants stimulate increased intracellular cAMP levels in PMNs. Our data, however, indicate that this receptor does not activate membrane-bound adenylate cyclase via direct nucleotide regulatory protein (N) coupling but instead raises cAMP levels indirectly via a mechanism which appears to require Ca2+ mobilization. This conclusion is based on the following data: 1) prostaglandin E1 (PGE1) activated and alpha 2-adrenergic treatment inhibited adenylate cyclase activation in PMN plasma membranes; fMet-Leu-Phe, however, neither activated nor inhibited adenylate cyclase in these membranes; 2) depletion of extracellular Ca2+ had no effect on isoproterenol and PGE1 elicited cAMP responses in intact PMNs while peak fMet-Leu-Phe and A23187-induced responses were reduced by approximately 50 and 80%, respectively; 3) 8-(N,N-diethylamino)-octyl-3,4,5-trimethoxybenzoate, a purported Ca2+ antagonist, caused almost complete inhibition of fMet-Leu-Phe and ionophore-induced cAMP responses in intact cells but had no effect on PGE1 and isoproterenol; 4) alpha 2-adrenergic agonists inhibited PGE1 but not chemoattractant- or A23187-elicited cAMP responses in intact PMNs; and 5) pretreatment of cells with a phosphodiesterase inhibitor (isobutylmethylxanthine) greatly potentiated the PGE1 and isoproterenol cAMP responses but nearly abolished the peak fMet-Leu-Phe response. Thus, chemoattractants appear to utilize a novel mechanism to raise cAMP levels which appear to require Ca2+ mobilization and could be mediated in part through a transient inhibition of phosphodiesterases. We suggest that stimulation of PMN functions by chemoattractants may utilize an N-coupled process to generate a Ca2+ signal which could in turn raise intracellular cAMP levels indirectly and thereby provide negative regulation.

1-Methyl-3-isobutylxanthine↗