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Biomedical subjects

J Nolan

Publications and source records attributed to J Nolan.

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

Clinical utility of an international thyroid database.

Assessment of thyroid function is prone to errors from several sources. Confusion is most often due to inappropriate use of tests, especially in patients with acute non-thyroid illness. With these problems in mind we have designed an international prospective thyroid database in three countries, which registers clinical and laboratory data on new patients with suspected thyroid disease. An additional aim was to assess the use of a computerised decision support tool to interpret thyroid data. The database permits rapid access to temporal trends in thyroid tests, which is useful in monitoring therapy and in follow up for hyperthyroidism. Marked contrasts in local clinical practices have highlighted the challenge in providing a valid decision tool to serve all clinical needs. Experience with multi-centre databases such as this hold promise in the drive to coordinate the disciplines of laboratory analysis and clinical decision making.

Clinical Laboratory Information Systems↗
PubMed1993

Differing patterns of cardiac parasympathetic activity and their evolution in selected patients with a first myocardial infarction.

OBJECTIVES: The purpose of the study was to compare cardiac parasympathetic activity during the early and convalescent phases of acute anterior and inferior myocardial infarction. BACKGROUND: Previous studies have shown that cardiac parasympathetic activity may vary with the site of infarction and that recovery may occur after infarction. METHODS: Cardiac parasympathetic activity was measured from 24-h electrocardiograms by counting the number of times that successive RR intervals (counts) differed by > 50 ms. Recordings began within 12 h of admission and at 7, 42 and 140 days after acute myocardial infarction in 20 patients (mean age 57 +/- 7.9 years). All patients were treated with streptokinase, aspirin and oral beta-adrenergic blocking agents. RESULTS: For the entire group, mean total 24-h RR counts increased from 592 (range 78 to 3,812) at 48 h to 648 (range 109 to 5,473) at 7 days, 1,145 (range 162 to 6,268) at 42 days and 1,958 (range 344 to 9,632) at 140 days. Patients with anterior infarction had significantly lower counts (mean 277, range 78 to 2,708; n = 11) compared with those with inferior infarction (mean 2,172, range 897 to 3,812; n = 9) at 48 h (p < 0.05). There was no significant difference in counts between patients with anterior (mean 1,051, range 212 to 6,268) and inferior (mean 1,321, range 162 to 3,265) infarction after 42 or after 140 days (anterior: mean 1,655, range 344 to 9,632; inferior: mean 2,588, range 1,700 to 5,767). CONCLUSIONS: These data suggest that after anterior myocardial infarction there is impaired cardiac parasympathetic function that improves within 6 weeks, whereas in inferior infarction there is relative preservation of cardiac parasympathetic function.

Adult↗
PubMed1993

Protein turnover in two kangaroo sub-species (Macropus robustus robustus and M. r. erubescens) from divergent habitats and the sympatric feral goat (Capra hircus).

1. Whole-body protein turnover was measured by a single-injection [15N]glycine method in the euro (Macropus robustus erubescens), wallaroo (M. r. robustus) and goat (Capra hircus). 2. Dietary nitrogen (N) intake was greater (P < 0.05) in the goat (1.17 g N/kg 0.75 x day) than in the kangaroo sub-species and greater (P < 0.05) in the wallaroo (1.07 g N/kg 0.75 x day) than in the euro (0.93 g N/kg 0.75 x day). similar (0.29-0.34 g N/kg 0.75 x day) among the species. 3. Crude protein (CP) turnover was similar in the euro (14.8 g CP/kg 0.75 x day) and goat (13.8 g CP/kg 0.75 x day) and less (P < 0.05) in the wallaroo (10.4 g CP/kg 0.75 x day).

Animals↗
PubMed1993

Supraventricular tachycardia, right atrial pressure, atrial natriuretic peptide and polyuria--a necessary sequence?

The release of atrial natriuretic peptide (ANP) may be stimulated by tachycardia and the evidence from human studies suggests that this is mediated by a rise in atrial pressure. However, animal experiments suggest that tachycardia can by itself increase ANP levels without increasing right atrial pressure (RAP). We report here the case of a healthy volunteer who had supraventricular tachycardia (SVT) whilst participating in a study evaluating the relationship between changes in RAP and changes in ANP. The ANP levels rose following the SVT but there was no rise in RAP, suggesting that heart rate can modulate ANP levels without changes in RAP as has been shown in animal experiments.

Adult↗
PubMed1993

Local anesthesia in cataract surgery--a comparison of different methods.

Seven groups of thirty patients undergoing cataract extraction under local anesthesia were each given different combinations of local anesthesia. These varied from a maximum approach using supra-orbital, infra-orbital and facial blocks with Hyalase, orbital compression and pre-operative Acetazolamide down to a minimum group receiving purely an infra-orbital and supra-orbital block with a Lignocaine/Bupivacaine mixture. There was no significant difference in local analgesia or in the complication rates between the seven groups. The benefits of Acetazolamide and orbital compression remain doubtful. The use of Hyalase and of a facial block resulted in fewer complications and in better akinesia.

Aged↗
PubMed1993

Heterocyclic mono-N-oxides with potential applications as bioreductive anti-tumour drugs: Part 1. 8-Alkylamino-substituted phenylimidazo [1,2-a] quinoxalines.

A series of imidazo [1,2-a] quinoxaline mono-N-oxides and their 6- and 9-aza analogues have been substituted in the 8-position with a variety of secondary and tertiary amines, and the compounds evaluated as bioreductively activated cytotoxins. Cytotoxic action against hypoxic cells in vitro was critically dependent upon the structural nature of the 8-substituent and its basicity, with little dependence upon reduction potential. 1,2-Dihydro-8-(4-methylpiperazin-1-yl)-4-phenylimidazo [1,2-a] pyrido [3,2-e] pyrazine 5-oxide (11) had differential hypoxic:oxic toxicity of 15.3 and some novel analogues had differential hypoxic:oxic toxicities of 7.5-17. Other related compounds with either substituted or unsubstituted 8-piperazinyl substituents, or certain straight-chain aminoalkyl substituents, show comparable activity in vitro. Less basic 8-substituents abolished activity, although the 8-morpholinyl derivatives (7 and 8) had differential hypoxic:oxic toxicities of 3-4. Substitution of the 4-phenyl ring with an electron-withdrawing group (F) improved hypoxic potency, but only with a small effect on hypoxic:oxic toxicity, whereas an electron-donating substituent (MeO) reduced hypoxic potency. Perhaps significantly, the 8-unsubstituted analogue 3 was 6-fold less potent, but had comparable differential cytotoxicity in vitro. The most effective novel hypoxia-selective cytotoxins synthesized were the bifunctional 2-nitro-imidazole derivative 1,2-dihydro-8-((4-(3-(2-nitro-1-imidazoyl)-1-hydroxypropyl)- piperazin-1-yl))-4-phenylimidazo [1,2-a] quinoxaline 5-oxide bishydrochloride (37) and its 9-aza analogue 38. These compounds also exhibited the lowest aerobic toxicities in vitro of the new compounds.

Antineoplastic Agents↗
PubMed1992

Effect of captopril on cardiac parasympathetic activity in chronic cardiac failure secondary to coronary artery disease.

Thirty-two patients with chronic cardiac failure underwent 24-hour ambulatory electrocardiographic monitoring on 2 separate occasions: 20 patients before and during treatment with captopril, and 12 acting as controls. Heart rate variability was calculated by counting the number of times successive RR interval differences were greater than 50 ms (this measurement being a reliable index of cardiac parasympathetic activity). During treatment with captopril, group mean total counts increased to 1,032 (range 48 to 7,437) from 482 (range 23 to 6,120) (p = 0.002). There was no change in mean hourly waking or sleeping heart rates. In the control group, no changes were seen: group mean total counts on the first occasion were 340 (range 120 to 3,255) and on the second occasion 400 (range 154 to 3,300) (p = not significant). These results show that treatment with angiotensin-converting enzyme inhibitors increases cardiac parasympathetic activity in patients with chronic cardiac failure. This may be relevant to the improved prognosis of this group of patients when treated with angiotensin-converting enzyme inhibitors.

Adult↗
PubMed1992

Acute effects of intravenous phosphodiesterase inhibition in chronic heart failure: simultaneous pre- and afterload reduction with a single agent.

Intravenous phosphodiesterase inhibition with milrinone is known to have a beneficial effect on haemodynamics in chronic heart failure. Its effect on lower limb capacitance vessels has not been previously investigated. We have studied the effect of intravenous milrinone in 10 patients with severe chronic heart failure. Thirty minutes after commencement of treatment mean cardiac index had risen by 26% and pulmonary artery wedge pressure, systemic vascular resistance and right atrial pressure had fallen by 51, 24 and 89%, respectively (p less than 0.05 for all changes). These changes were maintained for the 2 h observation period with no evidence of tolerance and were accompanied by a 17% increase in venous volume (p less than 0.01) and a 42% increase in ejection fraction (p less than 0.001) at 30 min; at 120 min the improvement in ejection fraction had been maintained and a further increase in venous volume to 38% above baseline was evident. The increase in venous volume was strongly correlated with the decrease in mean pulmonary artery wedge pressure and mean right atrial pressure at 30 min and 2 h (r = -0.80 and -0.69 for mean pulmonary artery wedge pressure, r = -0.88 and -0.56 for mean right atrial pressure). Milrinone therefore has clinically important venodilating properties, in addition to its known effects as an arterial vasodilator and a positive inotrope.

Aged↗
PubMed1992

Retention of misonidazole in normal and malignant tissues: interplay of hypoxia and reductases.

Tritiated misonidazole (MISO) was injected intravenously (iv) into mice bearing five different tumors. At 24 hr the tumors were removed for analysis of bound MISO, and at the same time three normal tissues were removed (liver, labial gland, and esophagus). The labial gland and esophagus were selected as representatives of sebaceous and stratified squamous tissues, respectively, tissues that in many parts of the body retain high levels of MISO. The tumors used were early transplant generations of spontaneous mouse tumors of mammary gland, lung, and liver. The levels (mean +/- SEM) of MISO at 24 hr for the five tumors and three normal tissues, expressed as percentage of the injected dose per gram of tissue were: A110 (0.03 +/- 0.007), A114 (0.103 +/- 0.04), A150 (0.09 +/- 0.005), A167 (0.037 +/- 0.012), A168 (0.122 +/- 0.0016), esophagus (0.507 +/- 0.09), labial gland (0.125 +/- 0.013), liver (0.11 +/- 0.004). Histochemical examination of the normal tissues showed reductase activity in all three. In the esophagus and labial gland, inhibition of the reaction by dicumarol indicated the likely presence of the reductase DT-diaphorase which, by 2-electron transfer, can be expected to reduce MISO to a reactive, locally-binding metabolite, even in the presence of oxygen.

Animals↗
PubMed1992

The use of octadecyl-bonded microparticulate silica in the separation of free and bound fractions during saturation analysis of vitamin D metabolites.

The use of octadecyl-bonded microparticulate silica to separate free and bound fractions during the saturation analysis of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D has been investigated. A slurry of octadecyl-bonded silica in an appropriate incubation buffer was prepared and used in parallel with a conventional dextran-coated charcoal suspension in several assay procedures. Standard curves, non-specific binding and plasma values were compared. A competitive protein binding assay for 25-hydroxyvitamin D and two radioreceptor assays and one radioimmunoassay for 1,25-dihydroxyvitamin D were investigated. In most cases the octadecyl-bonded silica preparation gave the more favourable results; its action was rapid, time- and temperature-independent, and it produced low non-specific binding and higher B0 values in all the assays examined. It was in our hands easier to use than dextran-coated charcoal. The use of octadecyl-bonded silica is recommended as an efficient agent for the separation of free and bound fractions in the saturation analysis of vitamin D metabolites.

Animals↗
PubMed1992

Atrial myxoma: tumour or trauma?

A mass lesion developed in the right atrium at the site of a trans-septal puncture after percutaneous balloon dilatation of the mitral valve in a man aged 74. The lesion had the pathological appearance of an atrial myxoma and seemed to have developed after trauma to the intra-atrial septum. This case suggests that at least some atrial myxomas are reactive rather than neoplastic in origin.

Aged↗
PubMed1992

Decreased cardiac parasympathetic activity in chronic heart failure and its relation to left ventricular function.

BACKGROUND: Activation of the sympathetic nervous system has been extensively studied in patients with chronic heart failure, but the parasympathetic nervous system has received relatively little attention. The objective in this study was to investigate cardiac parasympathetic activity in chronic heart failure and to explore its relation to left ventricular function. METHODS: Heart rate variability was measured from 24 hour ambulatory electrocardiograms by counting the number of times each RR interval exceeded the preceding RR interval by more than 50 ms (counts). This method provided a sensitive index of cardiac parasympathetic activity. RESULTS: Mean (range) of counts were: waking 48 (1-275)/h, sleeping 62 (0-360)/h, and total 1310 (31-7278)/24 h. These were lower than expected, and in 26 (60%) of the 43 patients counts fell below the lower 95% confidence intervals (95% CI) for RR counts in normal subjects. A significant correlation between total 24 hour RR counts and left ventricular ejection fraction was present (r = 0.49, p less than 0.05). CONCLUSIONS: These results indicate that most patients with chronic heart failure have reduced heart rate variability and therefore reduced cardiac parasympathetic activity. The degree of parasympathetic dysfunction is related to the severity of left ventricular dysfunction. This may be relevant to the high incidence of ventricular arrhythmias and poor prognosis of patients with chronic heart failure.

Adult↗
PubMed1991

Modulation of venous tone in heart failure.

Venodilatation may be an important property in drugs used to treat heart failure. Deductions about venous tone from standard hemodynamic studies may be misleading since filling pressures may be reduced by improved left ventricular function. To study the venodilator properties of drugs, we have modified a radionuclide blood pool method and shown that venous volume is increased by 10% after glyceryl trinitrate but is unchanged after the arteriolar dilator hydralazine. In patients with congestive cardiac failure, the calcium channel blocker, felodipine, causes a marked reduction in systemic vascular resistance and left ventricular filling pressures, but venous volume remains unchanged. In a similar group of patients comparable arterial and central effects are seen after the administration of captopril, but venous volume increases by 16%, and this increased venous volume is sustained after 3 months of long-term treatment. Milrinone has been used to treat both acute and chronic heart failure. As expected of a phosphodiesterase inhibitor, it exhibits inotropic properties in animals and humans and also causes arterial vasodilatation. We have studied its effects on venous tone in 10 patients with severe heart failure (New York Heart Association classes III to IV). Milrinone was given intravenously at a loading dose of 50 micrograms/kg followed by an infusion of 0.5 micrograms/kg/min. After treatment, cardiac index, which was measured by thermodilution, increased from 1.8 +/- 0.48 to 2.3 +/- 0.65 L/min/m2 (p less than 0.001); pulmonary artery wedge pressure fell from 23 +/- 6 to 11 +/- 5 mm Hg (p less than 0.001); and systemic vascular resistance index decreased from 4296 to 3168 dynes.sec.cm-5/m2 (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Captopril↗
PubMed1991

Factors influencing the transferability of medical decision support systems.

Transferability is a key issue in the development and implementation of medical decision support systems. Such systems have up to now tended to be confined to the development site. Transferability represents the integrated effect of several more basic attributes of Decision Support Systems. These attributes can be considered to belong to two main groups: those concerned with the Medical Domain (of the system) and those concerned with the Information Technology by which the System functions. Among the Domain issues the most important are: Epidemiology, Terminology and Methodology. Concerning the Information Technology issues the most important are: Knowledge Acquisition and Representation methods, Database design and integration with inference mechanism. The effect of each of the individual factors is considered by illustrations from the literature and by studying the results of recent experiments where databases and decision support systems from different countries are interchanged. This exercise allows some planning in the design of future systems with the aim of improving overall transferability and therefore applicability.

Artificial Intelligence↗