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Biomedical subjects

D R Lewis

Publications and source records attributed to D R Lewis.

At least 19 recordsLinked to original sources
PubMed1999

The pharmacokinetics of a single dose of gentamicin (4 mg/kg) as prophylaxis in cardiac surgery requiring cardiopulmonary bypass.

BACKGROUND: Cardiopulmonary bypass has complex effects on drug pharmacokinetics, which is important when considering the use of once-daily aminoglycoside regimens during cardiac surgery. AIM: To study the effects of cardiopulmonary bypass on the pharmacokinetics of a single dose of gentamicin (4 mg/kg). PATIENTS AND METHODS: Nine patients undergoing valve replacement surgery were given a single dose of gentamicin (4 mg/kg) at induction of anaesthesia and blood was taken for assay at 0, O.5, 1, 1.5, 2, 2.5, 3, 4, 6, 10, 16, 22 and 24 h following administration. The mean (range) gentamicin Cmax was 18.7 (12.4-26.3) mg/litre. Three patients had concentrations of gentamicin after 24 h of > 1 mg/litre. During cardiopulmonary bypass, the mean (range) gentamicin half-life (t1/2) was 5.1 (2.0-15.1) h and post-bypass the t1/2 was 7.1 (3.0-13.9) h. CONCLUSION: There is significant correlation between the elimination t1/2 and length of cardiopulmonary bypass (r = 0.89, P < 0.01). These results suggest that gentamicin excretion is delayed following cardiopulmonary bypass so that with dose regimens of > 4 mg/kg there is a risk of toxicity.

Aged↗
PubMed1999

Improving cytological diagnosis and surgical management of parotid adenolymphoma.

BACKGROUND: The role of fine-needle aspiration cytology (FNAC) in the diagnosis and management of discrete parotid swellings remains controversial. Controlled enucleation can be appropriate with accurate preoperative diagnosis. This study (1985-1995) reviewed the role of FNAC in the diagnosis and surgical management of adenolymphoma. METHODS: Review of cytological smears by two observers concentrated on the features of infarction and squamoid metaplasia. Sensitivity, interobserver and intraobserver variation were evaluated statistically in a two-run 'blinded' analysis of 80 cytological slides from a variety of lesions. RESULTS: Of 222 epithelial neoplasms of the parotid, 33 were adenolymphomas. FNAC was performed before operation in 32, producing 34 slides, and a correct cytological diagnosis was made in 21 patients. Retrospective review of the 34 slides, to examine specific features of squamoid metaplasia and infarction, improved diagnostic accuracy. The reliability and reproducibility of cytodiagnosis was confirmed by analysis of interobserver and intraobserver agreement. The sensitivity was high (0.76-0.88). Controlled enucleation was performed in 12 patients and superficial parotidectomy in 11. There were no tumour recurrences. CONCLUSION: Attention to the features of squamoid metaplasia and infarction improves cytological diagnosis and directs appropriate surgical management.

Adenolymphoma↗
PubMed1999

Potassium uptake supporting plant growth in the absence of AKT1 channel activity: Inhibition by ammonium and stimulation by sodium.

A transferred-DNA insertion mutant of Arabidopsis that lacks AKT1 inward-rectifying K+ channel activity in root cells was obtained previously by a reverse-genetic strategy, enabling a dissection of the K+-uptake apparatus of the root into AKT1 and non-AKT1 components. Membrane potential measurements in root cells demonstrated that the AKT1 component of the wild-type K+ permeability was between 55 and 63% when external [K+] was between 10 and 1,000 microM, and NH4+ was absent. NH4+ specifically inhibited the non-AKT1 component, apparently by competing for K+ binding sites on the transporter(s). This inhibition by NH4+ had significant consequences for akt1 plants: K+ permeability, 86Rb+ fluxes into roots, seed germination, and seedling growth rate of the mutant were each similarly inhibited by NH4+. Wild-type plants were much more resistant to NH4+. Thus, AKT1 channels conduct the K+ influx necessary for the growth of Arabidopsis embryos and seedlings in conditions that block the non-AKT1 mechanism. In contrast to the effects of NH4+, Na+ and H+ significantly stimulated the non-AKT1 portion of the K+ permeability. Stimulation of akt1 growth rate by Na+, a predicted consequence of the previous result, was observed when external [K+] was 10 microM. Collectively, these results indicate that the AKT1 channel is an important component of the K+ uptake apparatus supporting growth, even in the "high-affinity" range of K+ concentrations. In the absence of AKT1 channel activity, an NH4+-sensitive, Na+/H+-stimulated mechanism can suffice.

Arabidopsis↗
PubMed1999

Drinking water arsenic in Utah: A cohort mortality study.

The association of drinking water arsenic and mortality outcome was investigated in a cohort of residents from Millard County, Utah. Median drinking water arsenic concentrations for selected study towns ranged from 14 to 166 ppb and were from public and private samples collected and analyzed under the auspices of the State of Utah Department of Environmental Quality, Division of Drinking Water. Cohort members were assembled using historical documents of the Church of Jesus Christ of Latter-day Saints. Standard mortality ratios (SMRs) were calculated. Using residence history and median drinking water arsenic concentration, a matrix for cumulative arsenic exposure was created. Without regard to specific exposure levels, statistically significant findings include increased mortality from hypertensive heart disease [SMR = 2.20; 95% confidence interval (CI), 1.36-3.36], nephritis and nephrosis (SMR = 1.72; CI, 1.13-2.50), and prostate cancer (SMR = 1.45; CI, 1.07-1. 91) among cohort males. Among cohort females, statistically significant increased mortality was found for hypertensive heart disease (SMR = 1.73; CI, 1.11-2.58) and for the category of all other heart disease, which includes pulmonary heart disease, pericarditis, and other diseases of the pericardium (SMR = 1.43; CI, 1.11-1.80). SMR analysis by low, medium, and high arsenic exposure groups hinted at a dose relationship for prostate cancer. Although the SMRs by exposure category were elevated for hypertensive heart disease for both males and females, the increases were not sequential from low to high groups. Because the relationship between health effects and exposure to drinking water arsenic is not well established in U.S. populations, further evaluation of effects in low-exposure populations is warranted.

Aged↗
PubMed1999

Vascular surgical intervention for complications of cardiovascular radiology: 13 years' experience in a single centre.

This study investigates incidence and outcome of iatrogenic vascular complications needing surgery in a single vascular unit serving interventional vascular radiology and interventional cardiology. Evolution of diagnostic and interventional cardiovascular radiology, along with the introduction of non-surgical therapies for such complications, may have influenced the number of vascular complications requiring emergency surgery. Vascular surgical data were collected from information prospectively entered on computerised database and case note review. Radiology data were collated from prospective entries in logbooks and computerised database. In all 24,033 cardiovascular radiological procedures were performed between 1984 and 1996 (61% cardiac), numbers increasing annually. During this period, 62 patients (40 peripheral; 22 cardiac) required emergency surgical intervention after radiological procedures. Mean age was 61.9 years (range 1-92 years), male to female ratio was 1:1. The absolute number of cases requiring surgical intervention peaked in 1989, subsequently reducing annually. Sites of vascular injury included common femoral artery (40), brachial artery (6), iliac artery (6), popliteal artery (5), other (5). A total of 87 vascular surgical operations was performed (range 1-6 operations per patient). Interventions included thrombectomy/embolectomy (29), bypass grafting (16), direct repair (27). Seven major amputations were performed (two bilateral). Mortality after surgery was 9.7%. Mean inpatient hospital stay was 11.3 days (range 0-75 days). A Poisson regression model indicates a 5% reduction in risk for each successive year of observation; however, this did not reach statistical significance (P = 0.16, 95% CI 12% decreased risk to 2% increased risk). The risk of surgical intervention after diagnostic or interventional cardiovascular radiology is diminishing but still requires vigilance. Necessity for surgical intervention is associated with a high risk of morbidity and mortality.

Adolescent↗
PubMed1998

Physiological characterization of Taxol-induced large-fiber sensory neuropathy in the rat.

The cancer chemotherapeutic agent Taxol (paclitaxel) causes a dose-related peripheral neuropathy in humans. We produced a dose-dependent large-fiber sensory neuropathy, without detrimental effects on general health, in mature rats by using two intravenous injections 3 days apart. Tests of other dosing schedules demonstrated the dependence of the severity of the neuropathy and of animal health on both the dose and the frequency of dosing. Pathologically, severe axonal degeneration and hypomyelination were observed in sections of dorsal roots, whereas ventral roots remained intact. Electrophysiologically, H-wave amplitudes in the hindlimb and amplitudes of predominantly sensory compound nerve action potentials in the tail were reduced. These effects persisted for at least 4 months after treatment. Motor amplitudes were not affected, but both motor and sensory conduction velocities decreased. The ability of rats to remain balanced on a narrow beam was impaired, indicating proprioceptive deficits. Muscle strength, measured by hindlimb and forelimb grip strength, and heat nociception, measured by tail-flick and hindlimb withdrawal tests, were not affected by Taxol. This model of Taxol-induced neuropathy in mature rats, with minimal effects on general health, parallels closely the clinical syndrome observed after Taxol treatment in humans.

Animals↗
PubMed1998

Compression ultrasonography for false femoral artery aneurysms: hypocoagulability is a cause of failure.

OBJECTIVES: False femoral artery aneurysm is an occasional complication of percutaneous cardiovascular radiological procedures. Compression ultrasonography causes thrombosis non-invasively, reducing need for operative intervention. The technique fails in a proportion of cases. Analysis was undertaken to identify causes of failure. DESIGN: Prospective open study. MATERIALS AND METHODS: Patients presenting with false femoral artery aneurysm since 1984 were identified from a computerised database (BIPAS). Since 1993 compression ultrasonography has been performed as first line treatment according to a standard protocol. Prospectively collected ultrasonographic data and case notes were reviewed to identify causes of failed compression. RESULTS: False femoral artery aneurysm occurred as a complication in 32/26,687 (0.12%) cardiovascular radiological procedures. Eighteen aneurysms were treated by compression. The technique was successful in 11/18 (61%) cases but primary failure occurred in seven cases. Six out of seven had bleeding abnormalities (Chi-squared analysis with Yates correction 10.55, p = 0.0012), four were anticoagulated and compression was subsequently successful following reversal of warfarin therapy in three of these patients. In 4/18 cases surgical repair was necessary. CONCLUSION: Compression ultrasonography is an effective treatment of false femoral aneurysms, however, hypocoagulability is a significant cause of failure. For patients in whom anticoagulation cannot be reversed, primary surgical repair should be considered.

Aneurysm, False↗
PubMed1998

Sympathetic skin response and patient satisfaction on long-term follow-up after thoracoscopic sympathectomy for hyperhidrosis.

OBJECTIVES: To determine effect of sympathectomy for hyperhidrosis on sympathetic skin response (SSR) during long-term follow-up. Patient satisfaction was assessed and surgical complications noted. DESIGN: Prospective, Open, Non-randomised study. MATERIALS AND METHODS: Patients who had undergone bilateral thoracoscopic sympathectomy for hyperhidrosis underwent postoperative assessment of SSRs. A 15 mA stimulus was applied over the median nerve contralateral to the sympathectomy and evoked electrodermal activity was recorded from the sympathectomised palm using a Dantec Counterpoint Mk 2. Patient satisfaction with surgery was assessed by questionnaire and visual analogue score (0-1.0). RESULTS: Of 26 patients, 21 were female. Mean (range) age was 23 (9-36) years. Mean (range) follow up was 39 (4-138) months. 12% of cases had residual or recurrent symptoms. Median (range) patient satisfaction was 0.83 (0.06-1.0). In 7/52 palms recurrent SSRs were not detected. Repeated measures analysis of variance found amplitude of SSR to be of low significance with respect to time since surgery (F = 0.48; p = 0.49) and incidence of compensatory sweating (F = 2.38; p = 0.14). CONCLUSION: Thoracoscopic sympathectomy for hyperhidrosis is an effective procedure. Following sympathectomy SSRs are not permanently abolished, but return of SSRs does not correspond with symptom recurrence. As such, SSRs are a poor tool for objective assessment of long-term outcome following sympathectomy.

Adolescent↗
PubMed1998

The progression and correction of duplex detected velocity shifts in angiographically normal vein grafts.

OBJECTIVES: To review the sensitivity of duplex scanning and angiography at detecting vein graft stenoses in patients on a graft surveillance programme. DESIGN: Prospective, open, non-randomised study. PATIENTS AND METHODS: Since February 1993, 143 patients with 148 grafts (70% in situ, 30% reversed) have attended postoperative infrainguinal vein graft surveillance for a minimum of 6 weeks. Fifty-seven graft stenoses in 57 grafts were identified by duplex scanning as a localised high velocity jet. Angiography was performed in all except 12 patients. RESULTS: Angiography confirmed a duplex abnormality in all but 10 patients. Of these, five patients remain stable and asymptomatic with a persisting duplex abnormality. The remaining five patients, although asymptomatic, exhibited disease progression on duplex and surgical intervention confirmed significant stenoses, which were successfully treated. CONCLUSION: The results suggest that duplex scanning is a reliable imaging modality for detecting vein graft stenoses. Selection for surgical correction can be made, in some circumstances on the basis of clinical and ultrasound criteria alone.

Adult↗
PubMed1997

Antidepressant-like effect of brain-derived neurotrophic factor (BDNF).

Previous studies have shown that infusion of brain-derived neurotrophic factor (BDNF) into the midbrain, near the PAG and dorsal/median raphe nuclei, produced analgesia and increased activity in monoaminergic systems. Alterations in monoaminergic activity have also been implicated in the pathogenesis and treatment of depression. The present studies examined the ability of centrally administered BDNF to produce antidepressant-like activity in two animal models of depression, learned helplessness following exposure to inescapable shock and the forced swim test. In the learned helplessness paradigm, vehicle-infused rats pre-exposed to inescapable shock (veh/shock) showed severe impairments in escape behavior during subsequent conditioned avoidance trials, including a 47% decrease in the number of escapes and a 5 fold increase in escape latency, as compared to vehicle-infused rats which received no pre-shock treatment (veh/no shock). Midbrain BDNF infusion (12-24 micrograms/day) reversed these deficits, and in fact, BDNF-infused rats pre-exposed to inescapable shock (BDNF/shock) showed escape latencies similar to veh/no shock and BDNF/no shock rats. In the forced swim test, BDNF infusion decreased the immobility time by 70% as compared to vehicle-infused controls. Non-specific increases in activity could not account for these effects since general locomotor activity of BDNF- and vehicle-infused animals was not different. These findings demonstrate an antidepressant-like property of BDNF in two animal models of depression, which may be mediated by increased activity in monoaminergic systems.

Animals↗
PubMed1997

Computerised audit of carotid endarterectomy: audit loopholes closed?

The number of carotid endarterectomies being performed in the UK is increasing. The role of carotid endarterectomy (CEA) in the prevention of stroke depends on the procedure being associated with as few operative strokes as possible. Good clinical practice, with minimum morbidity, depends upon the integration of recent advances. Continuing audit has been used to examine changes in surgical practice and in case mix. There was a combined death and permanent stroke rate of 3.6% after 333 CEAs in a 6-year period (1990-1995) compared with 4.4% in 203 CEAs in an earlier 5-year audit period (1985-1989). The impact of an increase in the number of operations performed after recovered strokes, those performed by trainees and the use of prosthetic patches on the results of CEA has been assessed. Specific areas to be targeted in future audits are identified.

Adult↗
PubMed1995

Time course for entry of intestinally infused lipids into blood of rats.

The early time course of the absorption of duodenally infused 14C-labeled Intralipid into either the hepatic portal circulation or systemic circulation was measured. Plasma radioactivity did not increase significantly at either site until 30 min after the intestinal infusion began and was maximal between 60 and 120 min. In studies on the effects of intestinal lipid infusions on sham feeding in rats we find significant suppressions of sham feeding after only 10 min. Thus the time course for lipid absorption is different from that of the satiating effects of duodenally infused fats. These results are consistent with the hypothesis that the satiating effect of fats infused into the small intestine occurs before entry of absorbed fats into the blood and is not dependent on recently absorbed circulating fat.

Animals↗