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Biomedical subjects

M R Ellis

Publications and source records attributed to M R Ellis.

8 recordsLinked to original sources
PubMed1995

Mode of action of (R)-9-[4-hydroxy-2-(hydroxymethyl)butyl]guanine against herpesviruses.

The activity, metabolism, and mode of action of (R)-9-[4-hydroxy-2-(hydroxymethyl)butyl]guanine (H2G) against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) and varicella-zoster virus (VZV) were studied. Compared to acyclovir (ACV), H2G has superior activity against VZV (50% inhibitory concentration of 2.3 microM) and Epstein-Barr virus (50% inhibitory concentration of 0.9 microM), comparable activity against HSV-1, and weaker activity against HSV-2. The antiviral effect on HSV-1 showed persistence after removal of compound. H2G was metabolized to its mono-, di- and triphosphate derivatives in virus-infected cells, with H2G-triphosphate being the predominant product. Only small amounts of H2G-triphosphate were detected in uninfected cells (1 to 10 pmol/10(6) cells), whereas the level in HSV-1-infected cells reached 1,900 pmol/10(6) cells. H2G was a substrate for all three viral thymidine kinases and could also be phosphorylated by mitochondrial deoxyguanosine kinase. The intracellular half-life of H2G-triphosphate varied in uninfected (2.5 h) and infected (HSV-1, 14 h; VZV, 3.7 h) cells but was always longer than the half-life of ACV-triphosphate (1 to 2 h). H2G-triphosphate inhibited HSV-1, HSV-2, and VZV DNA polymerases competitively with dGTP (Ki of 2.8, 2.2, and 0.3 microM, respectively) but could not replace dGTP as a substrate in a polymerase assay. H2G was not an obligate chain terminator but would only support limited DNA chain extension. Only very small amounts of radioactivity, which were too low to be identified by high-performance liquid chromatography analysis of the digested DNA, could be detected in purified DNA from uninfected cells incubated with [3H]H2G. Thus, H2G acts as an anti-herpesvirus agent, particularly potent against VZV, by formation of high concentrations of relatively stable H2G-triphosphate, which is a potent inhibitor of the viral DNA polymerases.

Antiviral Agents↗
PubMed1994

Isolation of antirhinoviral sesquiterpenes from ginger (Zingiber officinale).

The dried rhizomes of Indonesian ginger, Zingiber officinale, were investigated for antirhinoviral activity in the plaque reduction test. Fractionation by solvent extraction, solvent partition, and repeated chromatography guided by bioassay, allowed the isolation of several sesquiterpenes with antirhinoviral activity. The most active of these was beta-sesquiphellandrene [2] with an IC50 of 0.44 microM vs. rhinovirus IB in vitro.

Antiviral Agents↗
PubMed1993

Coagulopathy screening in children with heparinized central venous catheters.

OBJECTIVE: To develop a method of screening for coagulopathy using blood drawn through heparinized central venous catheters. METHODS: Prothrombin time (PT) and activated partial thromboplastin time (APTT) were determined in paired blood samples with and without the addition of protamine, using an automated photo-optical method. A concentration of 4 micrograms/mL of citrated whole blood was chosen, based on preliminary experiments. This is sufficient to neutralize the expected heparin contamination in samples drawn through heparinized catheters while causing only a slight prolongation in APTT (due to the anticoagulant effect of protamine). Seventeen paired samples were drawn by venipuncture in patients without known coagulopathy. Twenty-five samples were drawn through heparinized central venous catheters. The first 5 mL of blood drawn from a catheter was discarded to avoid gross heparin contamination. Four samples from patients with coagulopathy were also analyzed with and without the addition of 2.5 micrograms/mL of heparin. RESULTS: Protamine increased PT by 9.0 +/- 0.8% and APTT by 9.0 +/- 3.4% (mean +/- SD) in the samples drawn by venipuncture. For samples drawn through heparinized catheters, 52% had a prolonged APTT, 44% a prolonged PT, and 68% had at least one prolonged test. With the addition of protamine, and after correction for the 9% mean increase in PT and APTT, 4% of samples had a prolonged APTT, 12% had a prolonged PT, and 16% had at least one prolonged test (P = .00006, .014, and .0001). All four samples from patients with coagulopathy were correctly identified as abnormal after the addition of protamine, with or without added heparin. CONCLUSIONS: A protamine-supplemented APTT test on blood drawn through a heparinized catheter may be an adequate screening test for coagulopathy. This procedure reduces discomfort in patients with an indwelling catheter by avoiding venipuncture.

Artifacts↗
PubMed1992

Colour-coded duplex ultrasonography in the selection of patients for endovascular surgery.

Endovascular surgery using angioplasty or atherectomy may potentially relieve the symptoms of claudicants with minimal morbidity, but results are best when short stenoses are treated. In this study, colour-coded duplex ultrasonography has been compared with angiography. In aortoiliac segments duplex examination had a sensitivity of 88 per cent and a specificity of 100 per cent; in femoropopliteal disease the sensitivity was 100 per cent and duplex scanning identified more disease than angiography. Subsequently, 73 symptomatic limbs with femoropopliteal disease were scanned to assess their suitability for endovascular surgery. Of these limbs, 27 (37 per cent) had suitable lesions and the remaining 46 (63 per cent) were spared angiography. Colour-coded duplex ultrasonography can reliably be used to select patients for endovascular surgery.

Aorta, Abdominal↗
PubMed1992

Prevalence, progression and natural history of asymptomatic carotid stenosis: is there a place for carotid endarterectomy?

The purpose of this study was to determine the prevalence, progression and prognosis of asymptomatic carotid artery stenosis in a population of 1198 patients with peripheral arterial disease (n = 986) or aortic aneurysm (n = 212), mean age 67.7 (S.D. = 10.0) years. Patients were recruited from 1985 to 1989 with annual assessment of carotid artery stenosis of over 50% using Doppler peak frequency analysis. Patients were followed up annually until 1990 or their first event, transient ischaemic attack (TIA), amaurosis fugax (AFx), stroke without antecedent TIA, or death (mean follow up 20 months). Life tables were used to determine risk of events in different patient groups. Only 164 (13.7%) patients had a stenosis of over 50% in either of the common or internal carotid arteries, disease was bilateral in 33 (2.8%) patients. A total of 33 patients (2.8%) had over 80% stenosis in common or internal carotid arteries. During follow up 37 (3.1%) patients developed a stenosis greater than 50%. Only 27 (2.3%) patients developed a stroke, 11 of which were fatal. A further 33 (2.8%) suffered a TIA or AFx and a total of 155 patients died during follow up. The total neurological event rate (TIA, AFx and stroke) was significantly associated with the presence of over 50% stenosis, [relative risk (RR) = 2.98, 95% confidence interval (95% C.I.) 1.68-5.29, p less than 0.001] and carotid bruit (RR = 1.16, 95% C.I. 1.23-3.81, p = 0.010). Although risk of stroke was higher in patients with a 50% stenosis, this failed to achieve statistical significance (RR = 1.78, 95% C.I. 0.66-4.80, p = 0.275).(ABSTRACT TRUNCATED AT 250 WORDS)

Aortic Aneurysm↗
PubMed1987

Management of asymptomatic carotid bruit.

One hundred forty-nine consecutive patients who had peripheral arterial disease (PAD) with clinically audible asymptomatic bruits were studied. Sixty-two of these patients were age- and sex-matched with 62 PAD patients in whom no bruits were detected. The PAD was demonstrated by angiography or by the 1-minute exercise test. Clinical assessment was performed every 6 months and oculoplethysmography and carotid phonoangiography (OPG/CPA) were performed every year. Angiography and reconstructive surgery were performed only if symptoms of transient ischemic attack (TIA) or stroke occurred. Life-table analysis revealed that over a 5.5-year follow-up, 32% of 211 PAD patients were expected to die. In the control study 45% of bruit patients and 32% of control patients were expected to die (no significant difference). Myocardial infarction accounted for 59% of deaths in the bruit group compared with 28% in the control group (no significant difference). TIA occurred more commonly in the bruit group (26.5%) than in the controls (6%) (p less than 0.02). However, stroke without warning occurred in 9% of bruit patients compared with 8% of controls (no significant difference). It is concluded that for asymptomatic carotid bruit it is safe to wait for the onset of symptoms before angiography and corrective reconstructive surgery.

Actuarial Analysis↗
PubMed1967

Chromatography.

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Chromatography↗