PubMed Health⌕ Search

Biomedical subjects

M G Evans

Publications and source records attributed to M G Evans.

At least 19 recordsLinked to original sources
PubMed2006

Impact of land drainage on peatland hydrology.

There is a long history of drainage of blanket peat but few studies of the long-term hydrological impact of drainage. This paper aims to test differences in runoff production processes between intact and drained blanket peat catchments and determine whether there have been any long-term changes in stream flow since drainage occurred. Hillslope runoff processes and stream discharge were measured in four blanket peat catchments. Two catchments were drained with open-cut ditches in the 1950s. Ditching originally resulted in shorter lag times and flashier storm hydrographs but no change in the annual catchment runoff efficiency. In the period between 2002 and 2004, the hydrographs in the drained catchments, while still flashy, were less sensitive to rainfall than in the 1950s and the runoff efficiency had significantly increased. Drains resulted in a distinctive spatial pattern of runoff production across the slopes. Overland flow was significantly lower in the drained catchments where throughflow was more dominant. In the intact peatlands, matrix throughflow produced by peat layers below 10 cm was rare and produced <1% of the runoff. However, in drained peatlands, matrix throughflow in deeper peat layers was common and provided around 23% of the runoff from gauged plots. Macropore flow, the density of soil piping, and pipeflow were significantly greater in drained peatlands than in intact basins. Gradual changes to peat structure could explain the long-term changes in river flow, which are in addition to those occurring in the immediate aftermath of peatland drainage.

England↗
PubMed2001

Safety profile of thalidomide after 53 weeks of oral administration in beagle dogs.

Fifty-six adult beagle dogs (28 male, 28 female) were orally administered thalidomide at 43, 200, or 1000 mg/kg/day for 53 weeks. Sixteen (2/sex/dose group) and 32 (4/sex/dose group) dogs were euthanized and necropsied after 26 and 53 weeks of dosing, respectively. The remaining 8 animals (2/sex/group; high-dose and control groups) were dosed for 53 weeks, euthanized, and necropsied at 58 weeks after a 5-week recovery period. There were no deaths during the study. The only observed clinical signs attributable to thalidomide administration were green-colored urine, white-colored fecal residue presumed to be unchanged thalidomide, enlarged and/or blue coloration of female mammary tissue, and prolonged estrus. There were no thalidomide-related changes in body weights, food consumption, electrocardiography, ophthalmoscopy, neurological function, and endocrine function. The mostly slight and/or transient variations observed in some hematology and blood chemistry values of dosed dogs were considered to be toxicologically insignificant and were supported by the lack of histopathologic correlates. The only gross finding attributable to thalidomide was a yellow-green discoloration of the femur, rib, and/or calvarium that was observed at each euthanization interval including recovery. There was no microscopic correlate for this finding. No thalidomide-related microscopic changes were seen in any of the organs and tissues at 26 weeks. Mammary duct dilatation and/or glandular hyperplasia observed in females at 53 and 58 weeks and hepatic bile pigment exhibited by high-dose males at 53 weeks were microscopic changes considered to be thalidomide-related. There was no gross and histopathologic evidence of any tumors. In summary, thalidomide at up to 1000 mg/kg/day for 53 weeks did not induce any major systemic toxicity or tumors in dogs. The NOAEL was 200 mg/kg/day.

Animals↗
PubMed2000

Fetus-in-fetu presenting as cystic meconium peritonitis: diagnosis, pathology, and surgical management.

Fetus-in-fetu (FIF), a rare congenital anomaly, is a fetus incorporating the well-differentiated tissue of its twin. The authors describe a newborn who presented with massive abdominal distension and severe respiratory distress. Abdominal x-rays showed multiple calcifications. The diagnosis of meconium pseudocyst was made. At emergency laparotomy an irregular fetiform mass was found in the retroperitoneum lying within a fluid-filled amniotic sac. It contained a vertebral column, 10 limblike structures, and cranial and caudal ends, supporting the diagnosis of fetus-in-fetu. This case highlights several important points. FIF often is overlooked in the differential diagnosis of a newborn abdominal mass and, as in this case, may be confused with meconuim pseudocyst. FIF should be differentiated from a teratoma because of the latter's malignant potential. Because this diagnosis is not made until pathological analysis, all parts of the mass should be removed to prevent malignant recurrence.

Abdomen↗
PubMed2000

Cholinergic control of membrane conductance and intracellular free Ca2+ in outer hair cells of the guinea pig cochlea.

We have studied the action of cholinergic agonists on outer hair cells, both in situ and isolated from the cochlea of the guinea pig, combining new fast CCD technology for Ca2+ imaging and conventional patch-clamp methods. Carbachol (1 mM) activated a current with a reversal potential near -70 mV and a bell-shaped I-V curve, suggesting that it was a Ca2+ activated K+ current. In a few cells, this current was preceded by a transient inward current, probably owing to an influx of Ca2+ and other cations through the acetylcholine (ACh) receptors. The amplitude of the Ca2+ signal was maximal in a circumscribed region at the basal pole of the cell and decreased steeply towards the apical pole, compatible with Ca2+ influx and/or Ca2+ induced Ca2+ release at the cells base. The time course of the Ca2+ rise was fastest at the base, but it was still slightly slower, and more rounded, than that of the K+ current. In some recordings the K+ current was observed without any measurable change of intracellular Ca2+. The K+ current was potentiated (18%) by caffeine (5 mM), and decreased (19%) by ryanodine (0.1 mM) in the majority of cells tested. The results are discussed in terms of a labile intracellular Ca2+ store located at the base of the cell, close to the Ca2+ permeable ACh receptor channels and Ca2+ activated K+ channels, whose contribution to the Ca2+ rise occurring in the region of the channels is variable, and probably dependent on its ability to refill with Ca2+.

Acetylcholine↗
PubMed2000

The behavioural outcomes of quality improvement teams: the role of team success and team identification.

This study investigates the relationship between hospital quality improvement (QI) team success and changes in empowerment, 'organizational commitment, organizational citizenship behaviour' (OCB) and job behaviour related to QI. Data were collected from administrative staff, healthcare professionals and support staff from four community hospitals. The study involved a field investigation with two data collection points. Structured questionnaires and interviews with hospital management were used to collect data on the study variables. High scores were observed for organizational commitment, OCB and job behaviour related to QI when individuals identified with teams that were successful. Low scores were observed when individuals identified with teams that were unsuccessful. Empowerment was positively related to job behaviour associated with QI. It is concluded that participation on QI teams can lead to organizational learning, resulting in the inculcation of positive 'extra-role' and 'in-role' job behaviour.

Health Services Research↗
PubMed1999

Measurement of staff empowerment within health service organizations.

A measure of empowerment was developed and its psychometric properties evaluated. Employees (n = 52) of two hospitals participated in semistructured interviews and a pilot test of the research instrument. A second study was undertaken with professional, support, and administrative staff (n = 405) of four community hospitals. Psychometric evaluation included factor analysis, reliability estimation, and validity assessment. Subjects responded to questionnaires measuring empowerment, leadership behavior, organizational citizenship behavior and job behaviors related to quality improvement. Factor analysis indicated three dimensions of empowerment: behavioral, verbal, and outcome empowerment. Coefficient alphas ranged from .83 to .87. The three dimensions were positively related to leadership behavior that encouraged self-leadership and negatively related to directive leadership. The three dimensions discriminated between the empowerment level of managers compared to that of nonmanagement staff. Empowerment predicted organizational citizenship behavior and job behaviors related to quality improvement.

Adult↗
PubMed1998

Kinetics of activation of a Ca2+-dependent K+ current induced by flash photolysis of caged carbachol in isolated guinea-pig outer hair cells.

It has been shown that the application of acetylcholine activates a Ca2+-dependent K+ current in outer hair cells, and the resulting hyperpolarization is thought to be an important part of the inhibition mediated by cholinergic efferent nerve fibres to the cochlea. In order to study the kinetics of the current, flash photolysis has been used to apply a cholinergic agonist, carbachol, rapidly to isolated outer hair cells. A delay in the onset of the outward potassium current following photorelease of carbachol was consistently observed, and the activation phase of the response could be described by a sigmoidal-like function with a mean delay of 59 ms and time constant of 71 ms. The sum of these values lies within the time scale reported for the onset of the inhibition following electrical stimulation of the efferent nerves. Although a distinct current attributable to an acetylcholine receptor was not visible in these experiments, indirect evidence for a carbachol-induced influx of Ca2+ was obtained.

Animals↗
PubMed1996

Acetylcholine activates two currents in guinea-pig outer hair cells.

1. Whole-cell voltage clamp recordings were made from outer hair cells (OHCs) isolated from the basal and middle regions of the cochlea. The current produced when acetylcholine (ACh) was applied to the basal pole was investigated. 2. Acetylcholine (50-70 microM) activated an early inward current followed by a late outward current in most cells at -70 mV. The activation of the early current was very rapid, with no delay. 3. The late outward current was a K+ current and was the major component of the total ACh-sensitive current at negative voltages. 4. The ACh-sensitive current was voltage dependent. From tail current measurements, the current was maximal at -55 mV and declined steeply at more positive potentials. On average, 50% of the current was active at -22 mV and 10% was active at 0 mV. This decline was caused by a reduction in the K+ current with depolarization. Between +20 and +40 mV, the major component of the ACh-sensitive current was the early current. 5. The steady-state I-V curve for the ACh-sensitive current was N-shaped, with a peak at -36 mV. The instantaneous I-V curve for the ACh-sensitive current taken from measurements just after a voltage step was outwardly rectifying and did not show this peak. This difference occurred because the voltage dependence was time dependent. 6. The reversal potential for the early current was estimated to be close to+13 mV, in accordance with it being a non-specification current. 7. The K+ current was abolished by the removal of external Ca2+. The effect occurred with no measurable delay. When external Ca2+ was lowered to 0.4 mM, the peak of the steady-state I-V curve for the ACh-sensitive current shifted by up to -20 mV and its amplitude was reduced. These results suggested that the K+ current was dependent on Ca2+ influx. 8. The inward current usually remained when the K+ current was abolished or greatly reduced by removing external Ca2+ or by dialysing the cells with BAPTA (5-10 mM). 9. Both early and late currents were reversibly blocked by alpha-bungarotoxin (0.2 microM) and curare (1 microM). 10. A simple scheme is proposed to account for the response. ACh, binding to a nicotinic receptor, directly gates the early cation current. Part of this current is carried by Ca2+, which once inside the cell leads to the activation of a Ca(2+)-dependent K+ current.

Acetylcholine↗
PubMed1996

Water soluble inhibitors of topoisomerase I: quaternary salt derivatives of camptothecin.

Eleven water soluble 7-substituted quaternary ammonium salt derivatives of 10,11-(methylenedioxy)- and 10,11-(ethylenedioxy)-(20S)-camptothecin were synthesized via the Friedlander reaction followed by nucleophilic displacement with an aromatic amine. All of these compounds were more potent than camptothecin in the in vitro cleavable complex assay. These inherently charged camptothecin derivatives were cytotoxic against three different human tumor cell lines (SKOV3, an ovarian adenocarcinoma; SKVLB a multidrug resistant ovarian adenocarcinoma; and HT-29, a colon carcinoma). A selected group of five compounds was evaluated in the nude mouse HT-29 xenograft model. Two of these quaternary salts (17 and 18) were more efficacious than Topotecan in delaying tumor growth. In an extended in vivo model, 18 demonstrated tumor regression.

Adenocarcinoma↗
PubMed1996

Hydrops fetalis and pulmonary sequestration.

The development of fetal hydrops in conjunction with intrathoracic pathology has been described, but rarely in association with pulmonary sequestration. The current report presents three cases of antenatally identified nonimmune hydrops fetalis, seen in association with pulmonary sequestrations. In one case, a left-sided chest mass also was defined. One infant was born by emergency cesarean section because of fetal distress at 34 weeks' gestation; the other two were delivered vaginally at 30 and 36 weeks. Two of the newborns were severely hydropic and required aggressive cardiorespiratory resuscitation that included bilateral chest tubes for massive pleural effusions. The third infant was stable at the time of birth, but thereafter respiratory distress developed, and intubation and ventilation became necessary. Two of the infants had a left-chest mass and the other had a right-sided mass, all identified by chest x-ray. Subsequent ultrasonography showed a chest mass and an identifiable systemic feeding artery in two of the patients. For the third, a specific diagnosis was not made before surgery. After resolution of hydrops, all three infants had successful removal of their intrathoracic pulmonary sequestrations. Two of these were found to be extralobar, and the other was an intralobar sequestration of the left lower lobe.

Adult↗
PubMed1996

Optimal elective management of patent ductus arteriosus in the older child.

Open surgical ligation has proven to be a safe and effective method to bring about closure of the patent ductus arteriosus (PDA). Recent studies have suggested that percutaneous transcatheter and video-assisted thorascopic closure may be better and more cost-effective techniques for PDA closure. The authors reviewed their experience with open thoracotomy for the elective ligation of PDA in 42 children over a 3-year period. The male:female ratio was 1.6:1; the age of the patients (mean +/- SD) was 2.8 +/- 2.3 years and their weight was 14 +/- 7 kg. In all cases the diagnosis was confirmed preoperatively by echocardiography. Open ligation of the PDA was performed through a limited left posterolateral thoracotomy with exposure, by an extrapleural approach. Closure was established with two silk ligatures or a silk ligature and clip, and drainage of the extrapleural space was not used. The operating time was 85 +/- 12 minutes. The total duration of hospitalization was 3.1 +/- 0.8 days. There were no deaths. Successful closure was confirmed by auscultation in 39 children and by subsequent echocardiography in three patients. No surgical complications occurred, and no transfusions were required. Minor respiratory symptoms occurred in two patients postoperatively. Transient systemic hypertension was seen in two patients, and one wound infection occurred.

Age Factors↗
PubMed1995

Synthesis and antitumor activity of novel water soluble derivatives of camptothecin as specific inhibitors of topoisomerase I.

The synthesis and antitumor activities of the novel water soluble camptothecin derivatives 7-[(4-methylpiperazino)methyl]-10,11-(methylenedioxy)-(20S)-campto thecin trifluoroacetate (6) and 7-[(4-methylpiperazino)methyl]-10,11-(ethylenedioxy)-(20S)-camptot hecin trifluoroacetate (7) are described. The solubilities of compounds 6 and 7 were measured to be 4.5 and 5.8 mg/mL, respectively, in pH 5 acetate buffer in contrast to < 0.003 mg/mL for camptothecin in the same buffer. In the purified topoisomerase I cleavable complex enzyme assay, compounds 6 and 7 demonstrated potent inhibition of topoisomerase I with IC50's of 300 and 416 nM, respectively, in comparison to 679 nM for camptothecin and 1028 nM for topotecan. In human tumor cell cytotoxicity assays, compounds 6 and 7 demonstrated potent antitumor activity against ovarian (SKOV3), ovarian with upregulated MDRp-glycoprotein (SKVLB), melanoma (LOX), breast (T47D), and colon (HT29) with IC50's ranging from 0.5 to 102 nM. Compounds 6 and 7 induced tumor regressions in the HT29 human colon tumor xenograft model and demonstrated similar rank order of potency compared to in vitro assay results.

Animals↗
PubMed1995

In vivo antitumor activity of two new seven-substituted water-soluble camptothecin analogues.

The development of camptothecin-like compounds as inhibitors of topoisomerase I for the treatment of resistant tumors has generated clinical excitement in this new class of drugs. We have developed two novel water-soluble camptothecin analogues which are specific inhibitors of topoisomerase I and are potent cytotoxins with significant antitumor activity. We added water-solubilizing groups off position 7 in the B ring of either 10,11-ethylenedioxy- or 10,11-methylenedioxy-20(S)-camptothecin. These water-soluble camptothecin analogues were demonstrated to be nanamolar inhibitors of the topoisomerase I enzyme in the cleavable complex assay. The compounds, GI147211 [7-(4-methylpiperazinomethylene)-10,11-ethylenedioxy-20(S)-camp tot hecin], and GI149893 [7-(4-methylpiperazinomethylene)-10,11-methylenedioxy-20(S)-cam pto thecin], were compared to topotecan, a known water-soluble inhibitor of topoisomerase I. Both GI compounds were found to be slightly more potent than topotecan as inhibitors of topoisomerase I in the cleavable complex assay and were 1.5-2 times more soluble. Tumor cell cytotoxicity assays using 5 separate cell lines demonstrated that both GI compounds were 5-10 times more potent than topotecan, although by comparison all three topoisomerase I inhibitors were unaffected by the multidrug resistance P-glycoprotein. The antitumor activity of all three topoisomerase I inhibitors was compared concomitantly in two human colon xenograft models. In both models, GI147211 and GI149893 were able to induce regression of established HT-29 and SW-48 colon tumors by as much as 60%. The antitumor activity of both compounds were also demonstrated in the MX-1 and PC-3 xenografts. Microscopic examination of selected tissues indicated that drug-induced toxicity was primarily limited to the gastrointestinal tract and was comparable among the three compounds. Further clinical development of this class of compounds is ongoing.

Animals↗
PubMed1995

Subchronic inhalation toxicity of 1,1,1,3-tetrachloropropane in rats.

The purpose of this study was to evaluate the inhalation toxicity of 1,1,1,3-tetrachloropropane (TCP), an intermediate in the production of chlorinated silicone fluids. Male and female Sprague-Dawley rats were exposed 6 hr/day, 5 days/week, for 90 days to TCP at concentrations of 0, 25, 75, or 225 ppm (Phase I study) and to 0, 1, 5, or 10 ppm (Phase II study). Phase II of the study was conducted because a no-observed-effect level was not achieved in Phase I. No animals died during the study. Clinical signs of toxicity included oral, nasal, and/or ocular discharge. No statistically significant differences were observed in either body weights or food consumption between exposed and control animals. Clinical pathology did not indicate any treatment-related effects. Absolute and relative liver and kidney weights were increased in male and female rats exposed to 225 ppm TCP, and heart weights were increased in male rats exposed to 225 ppm TCP. The liver and heart weight changes were supported by the findings of microscopic lesions in these organs. These lesions consisted of multifocal/focal myofiber degeneration necrosis with adjacent chronic myocarditis in the heart and multifocal single-cell necrosis in the liver parenchyma. The liver lesions had essentially resolved at the end of a 28-day recovery period but the heart lesions were still present in male rats in the recovery group exposed to 225 ppm TCP. No treatment-related effects were observed in animals exposed to 1, 5, or 10 ppm TCP.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1993

Spontaneous ovarian choriocarcinoma, yolk sac carcinoma, and teratoma in B6C3F1 mice: a case report.

Three ovarian neoplasms (choriocarcinoma, yolk sac carcinoma, and teratoma) were diagnosed in a 2 yr carcinogenicity study involving B6C3F1 mice. The yolk sac carcinoma and the teratoma occurred in opposite ovaries of a single female mouse that was sacrificed in extremis on study day 725. The choriocarcinoma occurred in a female mouse that was sacrificed in extremis on study day 565. These neoplasms were considered to be spontaneous in origin.

Animals↗