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Biomedical subjects

R Wootton

Publications and source records attributed to R Wootton.

At least 19 recordsLinked to original sources
PubMed1997

Diagnostic accuracy of teledermatology: results of a preliminary study in New Zealand.

AIM: To determine the accuracy of a video conferencing system (telemedicine) in diagnosis of dermatological disorders. METHODS: New patients referred to a dermatology clinic were initially examined by telemedicine and then by a standard face to face consultation. The diagnoses made by each type of consultation were compared and accuracy of telemedicine determined. RESULTS: One hundred and four patients with 135 dermatological conditions were analysed. Seventy five percent of conditions were correctly diagnosed by telemedicine. In a further 7% a differential diagnosis was made, which included the final diagnosis made face to face. In 12%, the diagnosis was incorrect using the telemedicine system, and in 3% no diagnosis was made. Four per cent of diagnoses were only made when the patient was seen face to face. CONCLUSION: This preliminary study suggests that video conferencing equipment can be used with a reasonable degree of accuracy for the diagnosis of dermatological disease.

Adolescent↗
PubMed1997

Comparison of the pharmacokinetics of lamotrigine in patients with chronic renal failure and healthy volunteers.

AIMS: The aim of this study was to compare the pharmacokinetics of the anti-epileptic agent, lamotrigine, in patients with chronic renal failure and healthy volunteers. METHODS: Non-compartmental pharmacokinetics of a single oral dose (200 mg) of the anti-epileptic agent, lamotrigine, and its main metabolite, lamotrigine N2-glucuronide, were determined for 10 patients with chronic renal failure of mean estimated creatinine clearance 18 ml min-1 and a control group of 11 healthy volunteers, matched for age and gender. RESULTS: For lamotrigine, there were no significant differences in Cmax, tmax, AUC, t1/2,z, CL/F and amount excreted in urine although t1/2,z tended to be longer for the renal failure group with a mean (+/-s.d.) of 35.9 +/- 10.7 h vs 27.8 +/- 4.3 h for the control group. For the renal failure group. VZ/F was 18% higher (95% CI 1% to 39%) compared with controls and CLR was reduced to 61% (95% CI 46% to 80%) of the control group value. For lamotrigine glucuronide, Cmax was increased 4-fold (95% CI 3.1 to 5.3) and AUC 7.8-fold (95% CI 6.0 to 10.1) in the renal failure group compared with controls. CLR was approximately 9-fold lower and apparent t1/2 was increased by 53% (95% CI 27% to 84%). Concentrations of an N2-methylated cardio-active metabolite, previously observed in dogs, were below the limit of detection (2 ng ml-1) of the ASTED/h.p.l.c. assay in the renal failure group as well as controls. CONCLUSIONS: These results indicate that impaired renal function will have little effect on the plasma concentrations of lamotrigine achieved for a given dosing regimen.

Administration, Oral↗
PubMed1997

The possible use of telemedicine in developing countries.

Telemedicine may be a useful technique for delivering health care in the developing world. However, there is little practical experience to draw on and real concerns that if additional resources were to become available telemedicine might not be the most appropriate use for them. The logical steps to determine the place of telemedicine in the developing world therefore appear to be: (1) to identify potential telemedicine projects-the Telecommunication Development Bureau of the International Telecommunication Union is trying to do this and has recently sponsored missions to various countries in Africa and Asia; (2) to carry out properly controlled pilot projects in order to demonstrate technical feasibility and to quantify the benefits to the healthcare system; (3) to calculate the costs of large-scale deployment. Assuming that telemedicine is shown to be beneficial, it is only at this final stage that a rational decision can be made about whether telemedicine would be an appropriate use of additional resources in a developing country, as opposed to alternative uses of those resources to solve other important problems of health care.

Delivery of Health Care↗
PubMed1997

Preliminary results from the Northern Ireland arms of the UK Multicentre Teledermatology Trial: effect of camera performance on diagnostic accuracy.

The diagnostic accuracy of realtime teledermatology was measured using two different video cameras. One camera was a relatively low-cost, single-chip device (camera 1), while the other was a more expensive three-chip camera (camera 2). The diagnosis obtained via the videolink was compared with the diagnosis made in person. Sixty-five new patients referred to a dermatology clinic were examined using camera 1 followed by a standard face-to-face consultation. A further 65 patients were examined using camera 2 and the same procedure applied. Seventy-six per cent of conditions were correctly diagnosed by telemedicine using camera 2 compared with 59% using camera 1. A working differential diagnosis was obtained in 12% of cases using camera 2 compared with 17% using camera 1. The percentage of 'no diagnosis', wrong and missed diagnoses was halved using camera 2 compared with camera 1. These results suggest that the performance of camera 2 was superior to that of camera 1 for realtime teledermatology.

Adolescent↗
PubMed1997

Effect of camera performance on diagnostic accuracy: preliminary results from the Northern Ireland arms of the UK Multicentre Teledermatology Trial.

The diagnostic accuracy of realtime teledermatology was measured using two different video cameras. One camera was a relatively low-cost, single-chip device (camera 1), while the other was a more expensive, three-chip camera (camera 2). The diagnosis obtained via the videolink was compared with the diagnosis made in person. Sixty-five new patients referred to a dermatology clinic were examined using camera 1 followed by a standard face-to-face consultation on the same day. A further 65 patients were examined using camera 2 and the same procedure implemented. Seventy-six per cent of conditions were correctly diagnosed by telemedicine using camera 2 compared with 62% using camera 1. A working differential diagnosis was obtained in 12% of cases using camera 2 compared with 14% using camera 1. The percentage of 'no diagnosis', wrong and missed diagnoses was halved using camera 2 compared with camera 1. These results suggest that the performance of the more expensive camera was superior for realtime teledermatology.

Dermatology↗
PubMed1996

Telemedicine: a cautious welcome.

Telemedicine is a major new development. Having become technically and economically feasible, it deserves proper investigation. Rushing into equipment purchase, however, is almost certain to prove counterproductive. Face to face contact is fundamental to health care and enthusiasts of telemedicine should recognise that it is not as good as the real thing (and unlikely ever to be). However, constraints on time and resources will make face to face consultation increasingly expensive, and telemedicine has the potential to produce major efficiencies in the diagnostic process. The goal of current research is therefore to marry medicine with technology, capitalising on the advantages of telemedicine and producing a robust system that delivers an acceptable service at an appropriate price.

Computer Communication Networks↗
PubMed1996

Inhibition of dihydropyrimidine dehydrogenase by 5-propynyluracil, a metabolite of the anti-varicella zoster virus agent netivudine.

OBJECTIVE: To study the effects of the anti-herpetic drug netivudine on dihydropyrimidine dehydrogenase activity in elderly volunteers and to relate them to concentrations of netivudine and its metabolite 5-propynyluracil. METHODS: Three groups of eight elderly volunteers received 400 or 800 mg netivudine or placebo once daily for 8 days. Plasma netivudine, 5-propynyluracil, and uracil, an indirect measure of dihydropyrimidine dehydrogenase activity, were assayed before the first dose and on days 2, 3, 5, 7 and 8. Full plasma profiles of netivudine and 5-propynyluracil were determined after the last dose. RESULTS: Plasma uracil was unquantifiable in all subjects before the first dose and at all time points in the placebo group. In recipients of netivudine it reached a plateau between days 3 and 5, with mean values of 23.2 and 23.5 mumol/L on day 8 in the subjects who received 400 and 800 mg. Plasma netivudine concentrations were approximately dose proportional, but 5-propynyluracil concentrations were similar in both groups. The half-maximal rise in plasma uracil occurred after a cumulative 5-propynyluracil exposure of 120 mumol/L.hr; such exposures will be achieved even after doses as low as 50 to 100 mg daily. CONCLUSIONS: Netivudine dosing produces complete inhibition of plasma dihydropyrimidine dehydrogenase. Coadministration with the antimetabolite 5-fluorouracil will require a substantial reduction in 5-fluorouracil dose to avoid toxicity but may also improve the therapeutic index of 5-fluorouracil.

Aged↗
PubMed1996

Tucaresol increases oxygen affinity and reduces haemolysis in subjects with sickle cell anaemia.

The primary pathophysiological event in sickling is the intracellular polymerization of deoxygenated haemoglobin S. Tucaresol (589C80;4[2-formyl-3-hydroxyphenoxymethyl] benzoic acid), a substituted benzaldehyde, was designed to interact with haemoglobin to increase oxygen affinity and has been shown to inhibit sickling in vitro. We administered tucaresol to sickle cell patients in the steady state to examine the anti-sickling effect in vivo. Oral doses of tucaresol or placebo were given to nine stable sickle cell patients (aged 17-39 years; tucaresol, six; placebo, three) for 10 d. The first two patients on tucaresol were scheduled to receive a loading dose of 800 mg or 1200 mg (depending on bodyweight) for the first 4 d, followed by maintenance doses of 200 or 300 mg for the next 6 d. Due to concerns over the sharp rise in haematocrit in one patient, subsequent cohorts received 300 mg tucaresol daily throughout the dosing period. The oxygen affinity of haemoglobin S was increased in all patients receiving tucaresol, with between 10% and 24% of the haemoglobin modified, dependent on dose. In all patients on tucaresol, haemolysis was reduced with rises in haemoglobin of 0.9- 3.7 g/dl (mean 2.2 g/dl), falls in lactate dehydrogenase of 16-52%, and a halving of the irreversibly sickled cell counts. These effects were apparent within a few days and persisted for 1-2 weeks following discontinuation of the drug. Three of the six patients on tucaresol developed fever and cervical lymphadenopathy, with onset between days 7 and 11 from start of drug. Further evaluation of the tolerability and efficacy of tucaresol in sickle cell patients is necessary.

Adolescent↗
PubMed1996

Fetal telemedicine: six month pilot of real-time ultrasound and video consultation between the Isle of Wight and London.

DESIGN: Prospective audit of first six months. SETTING: Referral from a district general hospital on the Isle of Wight to a comprehensive tertiary referral service, the Centre for Fetal Care at Queen Charlotte's Hospital 120 km away in London. PARTICIPANTS: Women whose pregnancy was suspected, or at risk, of fetal abnormality. INTERVENTIONS: Remote consultation by transmitting ultrasound and video in real-time over ISDN 30 telephone lines. Contemporaneous questionnaire to referring practitioner and patient. MAIN OUTCOME MEASURES: Frequency, indication, technical success and duration of consultation. Qualitative and semi-quantitative image quality. Effect of teleconsultation on need for physical referral. RESULTS: Twenty-nine women underwent 39 teleconsultations, and image quality was sufficient for diagnosis in all but one. Fetal abnormalities were present in 76%. Referral in person was required for only four women, significantly fewer than the 13 the referring hospital indicated would have been physically referred in the absence of this service (P < 0.001). Most mothers were counselled by the specialist "face-to-face' over the link, and 80% felt teleconsultation reduced their anxiety. CONCLUSIONS: A fetal telemedicine service is technically and clinically feasible. This demonstration suggests that such a service reduces the need for physical referral while increasing the rate of consultation, allowing better selection of patients who might benefit from referral. Further evaluation in a variety of clinical settings is now indicated, along with cost-benefit analysis.

England↗
PubMed1996

An evaluation of telemedical support for a minor treatment centre.

A low-cost telemedicine link was established from an accident and emergency department in Belfast to support nurse practitioners running a minor treatment centre (MTC) in London. During the 12 months before the introduction of the telemedicine link, 6729 patients were seen in the MTC. Of these, 155 (2.3%) were referred to the nearest accident and emergency department and 802 (11.9%) were referred to their general practitioner (GP). During the first 12 months of the use of the telemedicine link, 9972 patients were seen in the MTC. Of these, 147 (1.5%) were referred to the accident and emergency department and 383 (3.8%) were referred to their GP. During the evaluation period, 51 patients were seen using the telemedicine link, representing 0.5% of all MTC attenders during that period. The total number of teleconsultations was less than expected. The reasons for this difference include random variation, but could also include confidence resulting from the presence of the link and a training effect. The telemedicine link for trauma and minor injuries was an extremely cost-effective way of providing medical expertise to cover the clinical risk of the 0.5-1.5% of the case load that required expert medical opinion. The direct costs of on-site medical staff would have been 50,000 pounds per annum, excluding overhead charges. The annual cost of the videolink, including overheads, was 7250 pounds, amounting to a saving of some 42,000 pounds per annum.

Emergency Medical Services↗
PubMed1996

Point-to-point telemedicine using the ISDN.

Two pilot telemedicine trials were established, one using basic-rate ISDN (minor injuries service) and one using primary-rate ISDN (remote fetal scanning). Preliminary results were most encouraging. In the first 10 months of operation, 49 patients with minor injuries were managed successfully using telemedicine. Preliminary calculations suggest that the use of a low-cost telemedicine link was extremely cost-effective in comparison with the cost of providing conventional medical cover. In the first six months of operation the fetal scanning link was used for 39 consultations in 29 patients. In 25 cases (86%) a definitive diagnosis was made using the telemedicine link and physical referral was avoided. However, the current cost of the required hardware (approximately 35,000 pounds per end) is likely to militate against the widespread introduction of the technique, especially since the principal savings are intangible from the perspective of any hospital considering purchase. From the point of view of its use as an information transport system for telemedicine, the ISDN proved reliable (only one failure to establish a connection on demand). Picture quality was acceptable in most cases.

Computer Communication Networks↗
PubMed1995

The bioavailability and disposition of 1-(beta-D-arabinofuranosyl)-5-(1-propynyl)uracil (882C87), a potent, new anti-varicella zoster virus agent.

1. The bioavailability and disposition of 882C87, an anti-varicella zoster virus (VZV) agent, have been investigated in healthy young and elderly volunteers. 2. The mean bioavailability of a 200 mg tablet was 21.1% in the young (range 13.3-33.0%, n = 10) and 24.6% in the elderly (range 14.4-38.4%, n = 8), which is sufficient to achieve plasma concentrations well above the IC50 for anti-VZV activity. 3. Plasma concentrations of 882C87 after 50 mg i.v. were higher in the elderly than in the young, associated with a significantly longer half-life (13.7 vs 11.8 h) and decreased renal clearance (0.11 vs 0.14 ml min-1 kg-1) and total clearance (0.15 vs 0.17 ml min-1 kg-1). 4. After intravenous administration, the main route of elimination of 882C87 was renal with 81.6% recovered unchanged in urine in the young and 71.2% in the elderly. The pyrimidine base, 5-propynyluracil (5-PU) was unquantifiable in plasma and only present in trace amounts in urine. 5. After oral administration to four healthy volunteers, only 17% of a dose of [14C]-882C87 was recovered unchanged in urine and 58% as 5-PU, with total recovery in urine accounting for 86% of the dose. There was a lag of 4-12 h before the appearance of 5-PU in plasma, peak concentrations were one-third to a half those of 882C87. The data suggest that 5-PU is formed from unabsorbed 882C87 in the gut lumen and then absorbed and excreted in urine. 6. 882C87 is a potential once daily treatment for shingles.

Administration, Oral↗
PubMed1995

Pharmacokinetics and pharmacodynamics of tucaresol, an antisickling agent, in healthy volunteers.

1. Tucaresol is an orally administered antisickling agent which increases the oxygen affinity of haemoglobin. 2. The pharmacokinetics, effects on moderate graded exercise and psychometric performance of tucaresol were examined in a double-blind, placebo-controlled, parallel groups study in 12 healthy men. 3. Three doses of tucaresol were given at 48 h intervals intended to modify 15, 25 and 32.5% of a subject's haemoglobin to a high affinity form (%MOD). 4. Mean peak %MOD was 34%. Mean Cmax values in plasma and erythrocytes were 81.4 and 1459 micrograms ml-1, respectively. 5. Heart rate, compared with baseline, increased in the tucaresol group with the greatest changes at the highest %MOD and workload. There were no differences between groups in psychometric test performance. 6. Three volunteers on active drug developed fever, rash and tender cervical lymphadenopathy with onset 7-10 days from the start of dosing, suggesting an immune mechanism. 7. The acute increase in oxygen affinity with tucaresol is physiologically well-tolerated, but the utility of tucaresol in the management of sickle cell disease will depend on the identification of a dosing regimen with a lower incidence of drug allergy.

Administration, Oral↗
PubMed1995

Pharmacokinetics and tolerability of single oral doses of 882C87, a potent, new anti-varicella-zoster virus agent, in healthy volunteers.

882C87 is a nucleoside analog with potent, specific activity against varicella-zoster virus. It is approximately seven times as potent as acyclovir with an in vitro 50% inhibitory concentration of 1 to 2 microM. The tolerability and pharmacokinetics of single doses of 882C87 have been investigated in a series of studies with healthy young and elderly adult volunteers. The young received 50 to 1,600 mg, and the elderly received 50 and 100 mg. Concentrations of 882C87 and its main metabolite, the pyrimidine base 5-(1-propynyl)uracil (5PU), in plasma and urine were assayed by an automated sequential trace enrichment of dialysate-high-performance liquid chromatography procedure, and noncompartmental pharmacokinetic parameters were derived from the data. Concentrations of 882C87 in plasma increased proportionally for doses of up to 400 mg, but after higher doses the increase was less than dose proportional. In young adults, after 200, 400, and 1,600 mg, the maximum concentrations of the drug in plasma were 9.0, 16.3, and 34.7 microM, respectively, and the areas under the concentration-time curve (AUC) from 0 h to infinity were 166.6, 333.7, and 822.9 microM.h, respectively. Elimination half-life was 11.3 to 13.0 h after 50 to 400 mg, increasing to 15.3 h after 1,600 mg, associated with a small decrease in renal clearance. In healthy elderly volunteers concentrations of 882C87 in plasma after 50 and 100 mg were similar to those in young adults after twice the dose; apparent clearance and renal clearance were significantly reduced, and half-life was significantly longer at 15 h. Administration of 882C87 with food produced a small, nonsignificant reduction in mean AUC from 0 h to infinity, but in subjects with a low fasting AUC there was an increase after food and in subjects with a high fasting AUC there was a decrease. Concentrations of 5PU in plasma were one-third to one-half those of 882C87 and, in most subjects, were not dose proportional. There was a lag of at least 5 h after dosing with 882C87 before 5PU was detectable in plasma.

Administration, Oral↗
PubMed1995

Absolute bioavailability and metabolic disposition of valaciclovir, the L-valyl ester of acyclovir, following oral administration to humans.

Valaciclovir (Valtrex), the L-valyl ester of acyclovir, is undergoing clinical development for the treatment and suppression of herpesviral diseases. The absolute bioavailability of acyclovir from valaciclovir and the metabolic disposition of valaciclovir were investigated with healthy volunteers in two separate studies. In a randomized, crossover study, 12 fasting healthy volunteers each received 1,000 mg of oral valaciclovir and a 1-h intravenous infusion of 350 mg of acyclovir. The mean absolute bioavailability of acyclovir was 54.2%, a value three to five times that obtained previously with oral acyclovir. A similar estimate of 51.3% was made from urinary recovery of acyclovir. In the second study, four fasting volunteers received a single oral dose of 1,000 mg of [14C]valaciclovir. The majority of plasma radioactivity was accounted for by acyclovir, with very low plasma valaciclovir concentrations (mean maximum concentration of drug in plasma = 0.19 microM), which were undetectable after 3 h postdose. By 168 h, more than 90% of the administered radioactive dose was recovered, with approximately 45% in urine and 475 in feces. More than 99% of the radioactivity recovered in urine corresponded to acyclovir and its known metabolites, 9-(carboxymethoxymethyl)guanine and 8-hydroxy-9- [(2-hydroxyethoxy)methyl]guanine, with valaciclovir accounting for less than 0.5% of the dose. Acyclovir, but no valaciclovir, was detected in fecal samples. These studies show that after oral administration to humans, valaciclovir is rapidly and virtually completely converted to acyclovir to provide a high level of acyclovir bioavailability in comparison with that following oral administration of acyclovir. The plasma acyclovir exposure obtained following oral administration of valaciclovir is similar to that achieved with doses of intravenous acyclovir, which are effective in the treatment and suppression of the less susceptible herpesviral diseases.

Acyclovir↗
PubMed1995

Selective retention of VLDL, IDL, and LDL in the arterial intima of genetically hyperlipidemic rabbits in vivo. Molecular size as a determinant of fractional loss from the intima-inner media.

To explore possible mechanisms whereby the triglyceride-rich lipoproteins IDL and VLDL may promote atherosclerosis, fractional loss of these lipoproteins from the intima-inner media was measured in vivo in genetically hyperlipidemic rabbits of the St Thomas's Hospital strain and compared with the fractional loss of LDL, HDL, and albumin. These rabbits exhibit elevated plasma levels of VLDL, IDL, and LDL. In each rabbit, two aliquots of the same macromolecule, one iodinated with 125I and the other with 131I, respectively, were injected intravenously on average 24 and 3 hours, respectively, before removal of the aortic intima-inner media. The fractional loss from the intima-inner media of newly entered macromolecules was then calculated. The average fractional losses for VLDL, IDL, LDL, HDL, and albumin in lesioned aortic arches were 0.1%/h (n = 4), -0.2%/h (n = 3), 1.8%/h (n = 4), 11.4%/h (n = 3), and 26.3%/h (n = 1), respectively; in nonlesioned aortic arches fractional losses for IDL, LDL, HDL, and albumin were 1.7%/h (n = 1), 0.6%/h (n = 2), 14.6%/h (n = 3), and 25.9%/h (n = 3). In both lesioned and nonlesioned aortic arches, the logarithms of these fractional loss values were inversely and linearly dependent on the diameter of the macromolecules (R2 = .57, P = .001 and R2 = .84, P < .001), as determined from electron photomicrographs of negatively stained lipoproteins. These results suggest that after uptake into the arterial intima, VLDL and IDL as well as LDL are selectively retained in comparison with HDL and albumin.

Albumins↗
PubMed1995

Fetal telemedicine: interactive transfer of realtime ultrasound and video via ISDN for remote consultation.

Current referral practice for ultrasonically detected fetal abnormalities contributes to parental anxiety, inconvenience to patients, diagnostic inaccuracy, and general service inefficiency. To determine whether telemedicine would reduce these disadvantages, we established a 30-channel ISDN link between a district general hospital on an island and a subspecialty referral centre approximately 120 km away on mainland Britain. Live ultrasound images of the fetus were transmitted in realtime from a commercial scanner in the hospital using a total data transfer rate of 2 Mbit/s. After decompression at the receiving end, there was almost no perceptible loss of picture quality or frame rate. This report describes the technical aspects of the link and our preliminary experience with it. In the first two months of its operation, the link worked well and the consultants who used it found themselves confidently making diagnoses and carrying out counselling over it. If confirmed, the success of this technology has implications for future referral practice in fetal medicine.

Artifacts↗