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Biomedical subjects

M Ellis

Publications and source records attributed to M Ellis.

At least 37 records · Page 2Linked to original sources

Effect of repeated dosing on the pharmacokinetics of oral fluconazole in bone marrow transplant patients.

We examined the pharmacokinetics of fluconazole in 11 bone marrow transplant patients after multiple oral daily dose of 200 mg of this drug. Blood was sampled at different intervals on day 1, day 13, and day 27. No dose was given on day 2, day 14, and day 28 to allow the concentration-time data to be collected over 48 hours. The 24 hour urine was also collected, and fluconazole was analyzed in both plasma and urine by a high performance liquid chromatography. The plasma concentration-time data were best described by the one-compartment model with first-order absorption. The overall inter-day change and the difference between day 1 and day 27 in the rate constant for absorption (ka), peak plasma concentration (Cmax), through plasma concentration (Cmin), time-to-peak (tmax), area-under-the-curve 0-24 (AUC0-24), rate constant for elimination (ka), mean residence time after oral administration (MRTor), and fraction of the dose excreted unchanged in urine 24 hours (fu24) were significant (P < or = 0.0029 and P < or = 0.01, respectively). However, the difference between day 1 and day 13 was significant (P < or = 0.05) only in ka, tmax, Cmax, Cmin, and AUC0-24, and between day 13 and day 27 was significant (P < or = 0.05) only in ka, Cmin, ka, and MRTor. There was no significant inter-day change in the renal clearance. The significant (P < or = 0.05) increases in Cmax, Cmin, and AUC0-24 after the dose given on day 13 as compared with day 1, and in Cmin on day 27 as compared with day 13 indicate that, in contrast to volunteers, the steady state condition was not reached on day 13 and possibly not on day 27 in these patients. This perhaps should be taken into account when prescribing fluconazole to seriously ill patients.

Adolescent

Correlation of adenosine thallium 201 perfusion patterns with markers for inducible ischemia.

To determine the frequency of true myocardial ischemia caused by hemodynamic, metabolic, and regional functional abnormalities after intravenous adenosine infusion in patients with coronary artery disease, 13 patients--11 with coronary artery disease--received intravenous adenosine and thallium 201 during cardiac catheterization. Intracoronary adenosine levels increased by an average of 9.4-fold over baseline. Of the 11 patients, all had > or = 70% stenoses with a mean number of redistribution defects per patient of 3.3 +/- 0.7. Only two (18%) patients had new wall motion abnormalities detected by echocardiography during adenosine infusion. Pulmonary capillary wedge pressure did not significantly rise (13 +/- 7 to 17 +/- 8 mm Hg, p= NS). Lactate production occurred in two patients. Coronary sinus oxygen saturation levels rose from 29% +/- 6% to 68% +/- 8%, consistent with less myocardial oxygen extraction. Thus, despite a high prevalence of defects detected by 201Tl, the prevalence of true myocardial ischemia in patients with coronary artery disease undergoing pharmacologic stress imaging with intravenous adenosine is low. Perfusion defects induced by vasodilator stress are predominantly caused by heterogeneity of flow reserve rather than true ischemia.

Adenosine

Duplex imaging findings predict stenosis after carotid endarterectomy.

PURPOSE: This study was performed to determine whether early duplex findings predicted restenosis after carotid endarterectomy. METHODS: One hundred ninety-two symptomatic patients who underwent carotid endarterectomy were studied with color duplex imaging at 1 day and 1 week after surgery to identify minor residual disease (causing < 50% stenosis), arterial kinking, and suture stricture, and to measure the external and luminal diameters of the carotid bulb and distal internal carotid artery. Patients were then observed prospectively with duplex surveillance for a median of 24 months to identify > 50% restenosis. RESULTS: Twenty-five stenoses > 50% of the operated carotid artery (13%) were identified, four at 1 day (residual) and 21 at a median follow-up of 6 months (restenosis). On multiple logistic regression analysis, > 50% restenosis was found to be associated with minor day-1 residual stenosis (p = 0.01) and with small luminal diameter of the distal internal carotid artery (p = 0.03) as measured 1 week after carotid endarterectomy. Life table analysis showed restenosis at 24 months to be more common for patients with below-median than patients with above-median carotid bulb external diameter (18% vs 5%, respectively; p = 0.01). CONCLUSIONS: Duplex scanning within a week of carotid endarterectomy identifies > 50% residual stenosis, in addition to minor residual 25% to 50% stenosis and small carotid dimensions, which are good predictors of > 50% restenosis at 6 months.

Adult

Clinical follow-up rather than duplex surveillance after carotid endarterectomy.

PURPOSE: The value of duplex surveillance and the significance of contralateral carotid disease after endarterectomy have been assessed. METHODS: Three hundred five patients were observed prospectively after carotid endarterectomy for a median time of 36 months (range, 6 to 96 months), with duplex surveillance performed at 1 day; 1 week; 3, 6, 9, and 12 months; and then each year after endarterectomy. RESULTS: Thirty patients (10%) had ipsilateral symptoms (13 strokes, 17 transient ischemic attacks [TIAs]) at a median time of 6 months (range, 0 to 60 months). Life table analysis demonstrated that ipsilateral stroke was equally common for patients who had > or = 50% restenosis (3% at 36 months) and those who did not (6% at 36 months, p > 0.5). Twenty-three patients (8%) developed symptoms (stroke 5, TIA 14) attributable to the contralateral carotid artery at a median time of 9 months (range, 0 to 36 months) after endarterectomy. By life table analysis, 40% of patients with 70% to 99%, 6% with 50% to 69%, 1% with < 50% contralateral internal carotid stenosis, and 5% with contralateral carotid occlusion at the time of endarterectomy had a contralateral TIA in the 36 months after endarterectomy (p < 0.01). However, contralateral stroke was not significantly more common for patients with severe contralateral internal carotid stenosis demonstrated at the time of endarterectomy (< 50% stenosis, 0%; 50% to 69%, 3%; 70% to 99%, 7%; occlusion, 6% stroke rate at 36 months). Seven of the 32 patients who developed progression of contralateral disease had a TIA, compared with 11 of 227 patients who did not develop progression of contralateral disease (p < 0.01). None of the 12 patients who progressed from a < 70% to a 70% to 99% contralateral stenosis had a stroke. CONCLUSIONS: After carotid endarterectomy restenosis is rarely associated with symptoms; contralateral stroke is rare and is not associated with progressive internal carotid artery disease suitable for endarterectomy. This study has shown no benefit from long-term duplex surveillance after carotid endarterectomy. Selective clinical follow-up of patients who have high-grade contralateral stenoses would appear more appropriate.

Carotid Artery, Internal

Dilatation of saphenous vein grafts by nitric oxide.

OBJECTIVES: To investigate firstly whether flow-dependent vasodilation is maintained in vein grafts, and secondly whether nitric oxide donors dilate vein grafts to improve the flow through graft stenoses. DESIGN, MATERIALS AND METHODS: The vasodilatation of mature patent vein grafts, in response to reactive hyperaemia and glyceryl trinitrate (GTN), was assessed by the change in external diameter using duplex ultrasonography. The severity (ratio of proximal systolic velocity, V1, to peak systolic velocity at the stenosis, V2, of vein graft stenoses was determined by duplex ultrasonography before and after 24 h of local application of GTN patches. RESULTS: In post-occlusion hyperaemia the diameter of patent distal vein grafts (n = 7) increased to a maximum of 112 +/- 1.9% of resting diameter after 2 min, p = 0.026. The diameter increased further to 117 +/- 2.5% of the resting value 5 min after oral GTN (n = 5), p = 0.007. The velocity ratio, V2/V1, through graft stenoses (n = 6) decreased by 20 +/- 5% after application of GTN patches, principally as a result of reduction in V2, mean difference 0.8, p = 0.15. The changes in response to GTN were more evident for proximal than distal vein graft stenoses. CONCLUSION: Flow-induced vasodilatation responses, which have been attributed to the endothelial release of nitric oxide, are maintained in patent vein grafts: the grafts dilate even further in response to GTN. The application of GTN patches close to a vein graft stenoses appears to reduce the velocity ratio through vein graft stenoses. GTN patches might be used to reduce the risk of graft occlusion when there is a delay between the detection and the treatment of haemodynamically significant graft stenoses.

Administration, Cutaneous

Pharmacokinetics of oral fluconazole when used for prophylaxis in bone marrow transplant recipients.

The pharmacokinetics of fluconazole was investigated in 20 bone marrow transplant patients following oral administration of 200 mg of this drug. Blood samples were collected from each patient at different time intervals within 48 h after the first dose, and fluconazole was measured in plasma by high-performance liquid chromatography with UV detection. Urine was collected from 14 of these patients and analyzed similarly. The plasma concentration-time data exhibited the characteristics of the one-compartment model with first-order absorption quite well. The means +/- standard deviations of half-lives for absorption and elimination, peak concentration, time to peak, mean residence time, apparent volumes of distribution, area under the curve, and apparent oral clearance observed in these patients were 2.84 +/- 1.34 h, 19.94 +/- 18.7 h, 4.45 +/- 1.86 microg/ml, 8.34 +/- 5.97 h, 39.57 +/- 20.5 h, 0.874 +/- 0.48 liter/kg, 156.0 +/- 60.6 microg x h/ml, and 0.0256 +/- 0.0138 liter/h x kg, respectively. The amount of fluconazole excreted in urine in 24 h was 67.1 +/- 83 mg, which represents 33.55% +/- 41.6% of the dose administered. Patients who developed hemorrhagic cystitis excreted significantly (P < or = 0.0094) more fluconazole in 24 h than did those who did not.

Administration, Oral

Feed intake pattern of group-housed growing-finishing pigs monitored using a computerized feed intake recording system.

The feed intake pattern and growth performance of boars, barrows, and gilts fed diets differing in lysine and protein content were measured on 120 crossbred pigs from 27 (SD 3.7) to 81.5 (SD 9.2) kg live weight. The pigs were housed in eight mixed-sex groups with five pigs of each sex in each group. They were fed from an electronic feed station that recorded individual meal sizes and the time and duration of visits to the feeder for each animal in the group. Four dietary treatments were compared. During the grower period (27 to 55 kg), diets ranged in lysine content form .98 to 1.31%; for the remainder of the study, lysine content was .88 to 1.18%. Barrows had a greater (P < .01) number of meals per day than the other two sexes (7.4 vs 7.0 vs 7.0 +/- .10, respectively), but there were no significant differences among sexes for daily feed intake or other feed intake traits. Daily feed intake increased with dietary lysine content, largely because of increased meal sizes resulting from longer feeder occupation times at each visit. Visits to the feeder were greatest between 0900 and 1100 and lowest between 2000 and 0400. Correlations between feeding pattern and growth traits were relatively low. Repeatabilities of feeding pattern traits were generally higher when measured over shorter time periods. These results suggest a change in feeding behavior with increasing dietary lysine levels and a relatively small effect of sex on feeding pattern for mixed-sex groups of 15 pigs fed from a single electronic feed station.

Analysis of Variance

Incubation temperature effects on physical characteristics of normal, dark, firm and dry, and halothane-carrier pork longissimus.

Pigs (n = 18) were selected to represent three different muscle conditions (six pigs per condition): normal: dark, firm, and dry; and halothane carrier. A 45-cm-long longissimus section was excised from each side of the carcass at 30 min postmortem and cut into six sections. Right side sections were assigned to the intermediate temperature incubation (23 degrees C), and left side sections were designated high temperature incubation (40 degrees C). Sections were randomly assigned to incubation times (0, 1, 2, 4, 6, or 8 h). The 0 h section from each incubation treatment was designated as a control and was placed directly into a 4 degree C cooler. Temperature and pH were evaluated on the control section and for each loin section a the end of the incubation time. Color (L*, a*, and b* values), percentage of purge loss, water-holding capacity, and drip loss were determined. Incubation treatment did not alter pH decline in dark, firm, and dry muscle; however, high temperature increased pH decline in normal and halothane carrier samples. Results suggest that there is a strong interaction between pH and temperature that affects pork quality attributes. High incubation temperature had a negative effect on most quality variables; however, muscle condition (normal or halothane carrier) had limited effects on muscle quality.

Animals

Induction of apoptosis by chlorodeoxyadenosine and dexamethasone in B-chronic lymphocytic leukemia.

Apoptosis, programmed cell death, occurs in a variety of cellular systems and in response to many different stimuli. In the present study we examined the ability of dexamethasone (Dex) and chlorodeoxyadenosine (2-CdA) to induce apoptosis in lymphocytes of patients with B-chronic lymphocytic leukemia (B-CLL). Lymphocytes of 29 untreated patients and 9 healthy controls were isolated and incubated for 24 hours in the presence or absence of either Dex (2 microM) (n = 15) or 2-CdA (3 microM) (n = 14). Following incubation the cells were harvested and their DNA extracted and analysed for internucleosomal DNA cleavage by UV illumination after electrophoresis on agarose slab gel containing ethidium bromide. In the Dex group, 10 patients showed dexamethasone independent spontaneous apoptosis appearing 24 hours after the start of incubation. These were the only instances of dexamethasone-enhanced apoptosis. Five patients showed no spontaneous or dexamethasone induced apopto sis. Of the 2-CdA group, 5 showed spontaneous apoptosis enhanced by 2-CdA. No spontaneous apoptosis was observed in the cells from 9 other patients, however, 2-CdA induced apoptosis in 8 cases in this group. This study shows that monitoring of apoptosis in CLL may provide important information regarding susceptibility of the cells to drug induced apoptosis.

Antineoplastic Agents, Hormonal

Carotid plaque characteristics and presenting symptom.

BACKGROUND: The importance of identifying features of carotid artery disease, in addition to degree of stenosis, which predict subsequent stroke is becoming increasingly clear. This study assessed the relationship between carotid plaque characteristics and presenting symptoms. METHODS: Some 285 symptomatic (transient ischaemic attack (TIA) 127, amaurosis fugax 58, transient stroke 15, established stroke 55, progressive stroke 11, crescendo TIA 19) and 65 asymptomatic patients were studied with colour-flow duplex imaging. All patients had 60-99 per cent internal carotid stenosis. Carotid plaque morphology (classified according to Gray-Weale) and plaque surface features were assessed. RESULTS: Plaque types I and II were more common in symptomatic patients (83 per cent versus 44 per cent; P < 0.0001). Plaque surface was classified as smooth (34 per cent), irregular (44 per cent) or ulcerated (22 per cent). Ulceration was also more common in symptomatic patients (23 versus 14 per cent; P = 0.04). In symptomatic patients there was no association between presenting symptom and plaque morphology or surface features (P = 0.9 and P = 0.8 respectively). On multiple regression analysis plaque morphology did not distinguish between patients who presents with stroke without warning and other symptomatic patients (who had TIA, amaurosis fugax, crescendo TIA or stroke with warning). CONCLUSION: There was an association between echolucent type I and II carotid plaques and the presence of symptoms but not their type. Plaque morphology was not characteristic in a subgroup of patients who had stroke without warning. Further prospective study of plaque morphology in asymptomatic patients might help identify high-risk groups.

Adult

Probes for narcotic receptor-mediated phenomena. 21. Novel derivatives of 3-(1,2,3,4,5,11-hexahydro-3-methyl-2,6-methano-6H-azocino[4,5-b]indol- 6-yl)-phenols with improved delta opioid receptor selectivity.

Derivatives of racemic and optically pure levorotatory 3-(1,2,3,4,5,11-hexahydro-3-methyl-2,6-methano-6H-azocino[4,5-b]in dol-6-yl)phenols containing methoxy substituents in the C10', C9', and C8' positions (compounds 9-11, respectively) were synthesized and characterized by spectroscopic and X-ray methods. The binding affinities for the mu, delta and kappa 1 opioid receptors and activity in the guinea pig ileum (GPI) and mouse vas deferens (MVD) functional bioassays were determined for these compounds. A methoxy substituent in the C8' position decreases the binding affinity for both the mu and delta receptors, while a C10' methoxy substituent has little effect on either binding affinity. Interestingly, a methoxy group at the C9' position in the levorotatory series provides compound (-)-10 which exhibits both enhanced in vitro affinity and selectivity for the delta opioid receptor relative to the unsubstituted derivative (-)-8 and is the most selective (mu/delta IC50 ratio 17.9, kappa 1/delta IC50 ratio 314) and highest affinity (IC50 3.7 nM) delta receptor ligand for this novel class of compounds. The results of the GPI and MVD bioassays are more dramatic and indicate that (-)-10 is an agonist for the delta receptor (IC50 49.0 nM) with substantial selectivity for the delta versus the mu receptor borne out by a GPI/MVD IC50 ratio of > 612.

Analgesics

Migration of persons with AIDS--a search for support from elderly parents?

In this paper we investigate the interstate migration of people with AIDS to Florida under the hypothesis that a significant proportion of these moves are made to access care and support from elderly parents. We present a variety of aggregate data to support this hypothesis. Data recording interstate moves to Florida show that over 19% of interstate migrants with AIDS chose small cities and largely rural counties as their destinations, places without well-developed medical and social service facilities beneficial to people with AIDS. Moreover, the highest in-migration rates are in counties with the greatest proportion of elderly people, who are mostly retirees from other states. A Poisson regression model of destination choice indicates that the attraction of places with a high proportion of the population over 65 is statistically significant, after controlling for other factors that may also draw migrants with AIDS. We infer from analysis of trends in migration flows, that some people with AIDS may be relocating to seek support from elderly parents.

Acquired Immunodeficiency Syndrome

Postnatal hypothermia and cold stress among newborn infants in Nepal monitored by continuous ambulatory recording.

AIMS: To describe the pattern of hypothermia and cold stress after delivery among a normal neonatal population in Nepal; to provide practical advice for improving thermal care in a resource limited maternity hospital. METHODS: The principal government funded maternity hospital in Kathmandu, Nepal, with an annual delivery rate of 15,000 (constituting 40% of all Kathmandu Valley deliveries), severe resource limitations (annual budget Pounds 250,000), and a cold winter climate provided the setting. Thirty five healthy term neonates not requiring special care were enrolled for study within 90 minutes of birth. Continuous ambulatory temperature monitoring, using microthermistor skin probes for forehead and axilla, a flexible rectal probe, and a black ball probe placed next to the infant for ambient temperature, was carried out. All probes were connected to a compact battery powered Squirrel Memory Logger, giving a temperature reading to 0.2 degree C at five minute intervals for 24 hours. Severity and duration of hypothermia, using cutoff values of core temperature less than 36 degrees C, 34 degrees C, and 32 degrees C; and cold stress, using cutoff values of skin-core (forehead-axilla) temperature difference greater than 3 degrees C and 4 degrees C were the main outcome measures. RESULTS: Twenty four hour mean ambient temperatures were generally lower than the WHO recommended level of 25 degrees C (median 22.3 degrees C, range 15.1-27.5 degrees C). Postnatal hypothermia was prolonged, with axillary core temperatures only reaching 36 degrees C after a mean of 6.4 hours (range 0-21.1; SD 4.6). There was persistent and increasing cold stress over the first 24 hours with the core-skin (axillary-forehead) temperature gap exceeding 3 degrees C for more than half of the first 24 hours. CONCLUSIONS: Continuous ambulatory recording identifies weak links in the "warm chain" for neonates. The severity and duration of thermal problems was greater than expected even in a hospital setting where some of the WHO recommendations had already been implemented.

Adult

Comparison of two cotside methods for the detection of hypoglycaemia among neonates in Nepal.

AIMS: To compare two cotside methods of blood glucose measurement (HemoCue and Reflolux II) against a standard laboratory method for the detection of neonatal hypoglycaemia in a developing country maternity hospital where hypoglycaemia is common. METHODS: 94 newborn infants and 75 of their mothers had blood glucose assessed on the same venous sample using three different methods in the Special Care Baby Unit and postnatal wards, Prasuti Griha Maternity Hospital, Kathmandu, Nepal: HemoCue and Reflolux II at the cotside; Roche Ultimate glucose oxidase method (GOM) in the laboratory. RESULTS: The mean (SD) values for blood glucose in newborn infants were GOM 2.5 (1.1) mmol/l; Reflolux II 2.1 (0.9); and HemoCue 4.2 (1.2). For mothers the values were GOM 5.3 (1.2) mmol/l; Reflolux II 3.6 (1.2); and HemoCue 5.6 (1.0). Bland-Altman plots showed that Reflolux II consistently underreads GOM blood glucose in neonates by 0.5 mmol/l (SD 0.7) and that HemoCue overreads glucose by 1.7 mmol/l (SD 0.8). For the detection of hypoglycaemia (< 2.0 mmol/l), Reflolux II achieved a sensitivity of 83%, a specificity of 62%, and a likelihood ratio of 2.2. HemoCue produced a sensitivity of 0% and a specificity of 100% using measured values. If 2.0 mmol were subtracted from all Hemocue values this rose to 81% and 68% and a likelihood ratio of 2.5. CONCLUSION: Although more accurate than Reflolux II for the measurement of blood glucose in mothers, HemoCue overreads glucose concentrations in neonates and is therefore potentially dangerous as a screening method for neonatal hypoglycaemia. Reflolux II is useful as a screening method for high risk infants (low birthweight, post-term) and could achieve a post-test probability of detecting hypoglycaemia in a high risk setting like Nepal of 50-60%.

Adult

Comparison of transverse and longitudinal real-time ultrasound scans for prediction of lean cut yields and fat-free lean content in live pigs.

Live animal real-time ultrasound scans and carcass measures were taken on 80 pigs comprising two sexes (42 barrows; 38 gilts) and two halothane genotypes (40 carriers and 40 negatives) that were slaughtered between 108 and 148 kg live weight. Transverse scans (TRUS), at right angles to the midline, were taken on right (RS) and left (LS) sides at the last rib. Longitudinal scans (LON) were taken 6.5 cm off the midline immediately anterior (ANT) and posterior (PST) to the last rib on both the RS and LS. Longissimus muscle depth and area and backfat thickness over the longissimus muscle were measured on TRUS. Backfat thickness and longissimus muscle depth were measured at each end of the LON. Backfat thickness and longissimus muscle measurements were taken at the 10th and last rib on the RS of the carcass. Carcasses were fabricated using standard techniques to establish lean cut yields and carcass soft tissue was chemically analyzed to determine fat-free lean contents. Stepwise regression analysis was performed to develop equations to predict the weights and percentages of lean cuts and fat-free lean. Fat and muscle measures taken from ultrasound scans were generally less accurate than last rib carcass measures at predicting composition. There was little difference in R2 for equations based on either TRUS or ANT/LON; however, PST/LON, generally, were less accurate than ANT/LON. Combining measurements from more than one scan gave little improvement in R2 compared with the best single scan. Estimates of sex bias for carcass composition prediction were small. Halothane genotype and carcass lean content biases were detected; equations derived from the pooled data tended to overestimate the lean content of negative pigs and fatter carcasses and underestimate the lean content of carrier animals and leaner carcasses.

Animals

Influence of slaughter weight on growth and carcass characteristics, commercial cutting and curing yields, and meat quality of barrows and gilts from two genotypes.

Pigs representing two crossbred genotypes, a breeding company hybrid (BCH) and a three breed cross (Hampshire x [Yorkshire x Duroc]) (HYD) were evaluated at five slaughter weights (SLW): 100, 115, 130, 145, and 160 kg. A total of 160 pigs were grown in like-sex (barrows [B] or gilts [G]), like-genotype groups, with four pigs/group, from 60 kg live weight. A corn-soybean meal-based diet was available on an ad libitum basis (15.8% crude protein, 3,300 kcal/kg ME). One-half of the pigs from each group (80 pigs) were slaughtered for carcass and meat quality evaluation. Genotype BCH grew faster, had lower backfat depths in the loin and lumbar regions, and a smaller loin eye area than HYD, but both groups had a similar gain:feed ratio. Few consistent genotype differences in cutting and curing yields and meat quality were observed. Differences between sexes for growth and carcass traits were generally in agreement with previous research; however, the magnitude of the differences was small. There were few nonlinear regressions involving SLW and limited differences between genotypes or sexes in the slopes of the linear regressions. Increases in SLW were associated with increases in feed intake, backfat depth and loin' eye area, and minimal changes in growth rate or gain:feed. Percentage of loin increased and ham, shoulder, and spare rib percentages decreased with slaughter weight. The weight of trimmed, boneless cuts increased with slaughter weight, but percentage trimmed, boneless cuts was reduced. Curing yields for belly increased with slaughter weight. Changes in meat quality with increasing slaughter weight were relatively small. Longissimus lumborum fat content increased and moisture content decreased with slaughter weight. These results suggest that modern genotypes can be slaughtered at live weights up to 160 kg with limited impact on growth performance, commercial meat yields, or meat quality characteristics.

Abattoirs