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Biomedical subjects

T Ellis

Publications and source records attributed to T Ellis.

At least 55 records · Page 3Linked to original sources

Wound metastases following laparoscopic and open surgery for abdominal cancer in a rat model.

The recent application of laparoscopic resection techniques to malignant disease has raised safety concerns due to metastasis to surgical access wounds. The significance and incidence of this problem are controversial. In the present study a rat model, in which an implanted tumour was lacerated, was used to investigate whether application of laparoscopic techniques for malignant abdominal disease leads to an increased risk of tumour dissemination and implantation within the peritoneal cavity, and abdominal wall wounds. Malignant cells were implanted into the abdominal wall of 42 rats, resulting 7 days later in the growth of a tumour measuring 20-25 mm in diameter. There were three control groups: no surgery (n = 6); blunt manipulation of the tumour laparoscopically (n = 6); and blunt manipulation of the tumour at laparotomy (n = 6). Twenty-four rats underwent surgical laceration of the tumour capsule at either laparoscopy (n = 12) or laparotomy (n = 12). All rats were killed 1 week later, and examined for macroscopic evidence of tumour metastasis. The abdominal surgical wounds were excised for independent microscopic examination by a histopathologist. Growth of the primary tumour was greater in rats that had an operation than in unoperated controls, and was greater after laparotomy. However, wound metastases were five times more likely after laparoscopic tumour laceration than after the same procedure through an open incision (ten of 12 rats versus two of 12, P = 0.0033). Wound metastases following laparoscopic tumour manipulation are an important and real problem, with significant implications for the application of laparoscopic techniques to excise malignant disease in humans.

Abdominal Muscles↗

Cross-linking of human placenta pi class glutathione S-transferase dimer by chlorambucil.

Interaction of chlorambucil and the glutathione-depleted human placenta pi class glutathione S-transferase (pi GST) results in the formation of a complex between the drug and the protein at physiological pH. This complex is not formed in the presence of glutathione or S-hexylglutathione. Molecular mass measurement of the reaction product using matrix-assisted laser desorption mass spectrometry indicates that one molecule of chlorambucil cross-links two subunits of the homodimeric protein. A combination of enzymic proteolysis, high performance liquid chromatography, and mass spectrometry reveals that chlorambucil alkylation occurs at cysteine 47 of one subunit and cysteine 101 of the second subunit. This result supports the idea that conformational changes occur in glutathione-depleted pi GST, which allow the bifunctional tether of chlorambucil to cross-link the two subunits of the protein.

Affinity Labels↗

Myelinoclastic diffuse sclerosis presenting as a mass lesion in a child with Turner's syndrome.

A rare case of myelinoclastic diffuse sclerosis (MDS), occasionally referred to as Schilder's disease, is reported in a child with Turner's syndrome. The child originally presented with a 3-week history of nausea, vomiting and frontal headaches. Magnetic resonance imaging showed a large, contrast-enhancing, right frontal lobe mass which was ultimately resected uneventfully. Complete laboratory investigations and pathological evaluation of the resected specimen verified the case to be MDS. The clinical presentation, laboratory evaluation, imaging characteristics and diagnosis are discussed in this review of the disease. The importance of including demyelinating diseases in the differential diagnosis for newly discovered mass lesions in the pediatric population is underscored by this case.

Brain Neoplasms↗

Lung injury following exposure of rats to relatively high mass concentrations of nitrogen dioxide.

Human inhalation exposures to relatively high mass concentrations of the oxidant gas nitrogen dioxide (NO2) can result in a variety of pulmonary disorders, including life-threatening pulmonary edema, pneumonia, and bronchiolitis obliterans. Inasmuch as most experimental studies to date have examined NO2-induced lung injury following exposures to near ambient or supra-ambient concentrations of NO2, e.g., < or = 50 ppm, little detailed information about the pulmonary injurious responses following the acute inhalation of higher NO2 concentrations that are more commensurate with some actual human exposure conditions is currently available. Described in this report are the results from a series of investigations in which various aspects of the inhalation toxicity of high concentrations of NO2 have been examined in laboratory rats. In the first component of our study, we characterized the kinetic course of development of lung injury following acute exposures to high concentrations of NO2 delivered over varying durations, and we assessed the relative importance of NO2 exposure concentration versus exposure time in producing lung injury. For a given exposure duration, the resulting severity of lung injury was found to generally scale proportionately with inhaled mass concentration, whereas for a given concentration of inhaled NO2, the magnitude of resulting injury was not directly proportional to exposure duration. Moreover, evidence was obtained that indicated exposure concentration is more important than exposure time when high concentrations of NO2 are inhaled. In a second component of our investigation, we assessed the pulmonary injurious response that occurs when NO2 is inhaled during very brief, 'high burst' exposures to very high concentrations of NO2. Such exposures resulted in significant lung injury, with the magnitude of such injury being directly proportional to exposure concentration. Comparisons of results obtained from this and the first component studies additionally revealed that brief exposures to the very high concentrations of NO2 are more hazardous than longer duration exposures to lower concentrations. In a third study series, we examined pre-exposure, exposure, and post-exposure modifiers of NO2-induced lung injury, including dietary taurine, minute ventilation, and post-exposure exercise. Results from these studies indicated: (i) dietary taurine does not protect the rat lung against high concentration NO2 exposure, (ii) the severity of acute lung injury in response to NO2 inhalation is increased by an increase in minute ventilation during exposure, and (iii) the performance of exercise after NO2 exposure can significantly enhance the injurious response to NO2.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Inhalation↗

Immunoreactivity to Yersinia enterocolitica antigens in patients with autoimmune thyroid disease.

Recent reports have suggested that Yersinia enterocolitica proteins encoded by a 72-kilobase virulence plasmid (known as release proteins and now identified as YOP2-5) are antigens recognized specifically by patients with Graves' disease and of potential etiological importance in this disorder. To examine this hypothesis, we evaluated immune responses to YOP in patients with autoimmune thyroid disease and in normal controls. Humoral responses to Yersinia were assessed using Western blots of crude Y. enterocolitica membrane proteins, Yersinia release proteins (YOP2-5), and human thyrocyte membranes. Twenty-four of 25 Graves' and 10 of 18 Hashimoto's patients showed reactivity with the release proteins, primarily the 67-, 46-, 36-, and 25-kilodalton bands. However, 17 of 24 normal subjects also demonstrated serological reactivity to the release proteins, and the pattern of reactivity of these sera was similar to that in the thyroid patients. No correlation was noted between serological reactivity to the release proteins and thyroid hormone levels. Patients and controls with serological reactivity to YOP also showed reactivity with Yersinia membranes. In addition to the serological studies, cellular immune responses were determined by peripheral blood mononuclear cell proliferation assays. Cellular reactivity to the release proteins was present in four of five Graves' and both Hashimoto's patients tested, but also in two of six nonthyroid illness patients with serological immunity to the release proteins. Intrathyroidal lymphocytes obtained from two Graves' patients demonstrated marked proliferation in response to the release proteins. These results indicate that there is no unique pattern of serological reactivity against Yersinia membranes or the release proteins in patients with autoimmune thyroid diseases and suggest that any causal relationship between Yersinia infection and Graves' disease may be related to T-cell immunity.

Antibodies, Bacterial↗

Phase II trial of recombinant human interferon alpha in myelodysplastic syndromes.

Twenty patients with myelodysplastic syndromes were treated with daily subcutaneous injections of interferon alpha 2a, at the initial dose of 3 x 10(6) U/m2. Hemogram, chemistry profile, natural killer (NK) cell activity and lymphokine-activated killer (LAK) cell cytotoxicity were monitored serially. Bone marrow with cytogenetic analysis was done before therapy and every three months afterwards. Normalization to the complete blood count, and wherever applicable, decrease in blast count of 5% or less were defined as a complete response. Improvement in hemoglobin level to 12 g/dl, neutrophil count to 1000/mm3 and platelets to 100,000/mm3 was considered a partial response. The median age was 71 (range 59-83) years and 16 of the patients were males. Two patients withdrew from the treatment in the first week and were considered ineligible. Among the other 18, two had refractory anemia, two refractory anemia with ringed sideroblasts, four chronic myelomonocytic leukemia, eight refractory anemia with excess blasts, and two refractory anemia with excess blasts in transformation to acute leukemia. Twelve patients were treated for six months, the other six were taken off the treatment after six to eight weeks because of disease progression. Only one patient with chronic myelomonocytic leukemia had a partial response for two months. NK cell activity remained unchanged before (18.3 +/- 4.6 lytic units) and during interferon therapy (19.6 +/- 5.3 lytic units). LAK cytotoxicity was not detected in any patient before therapy and was seen in only one patient (not the responder) during therapy (5.7 lytic units). The toxicity of the interferon therapy was substantial. Seventeen patients required a dose reduction and fifteen lost greater than 10% of body weight. Eleven patients (61%) developed infections requiring antibiotic therapy, and eight (44%) required hospitalization. Seven patients developed neurologic toxicity. Interferon alpha 2a is an ineffective but toxic therapy in these elderly patients with myelodysplastic syndromes.

Aged↗

MRI and diabetic foot infections.

The role of magnetic resonance imaging and plain radiographs in evaluating osteomyelitis in the diabetic foot was studied. Fifty patients were prospectively examined by magnetic resonance imaging and plain radiographs to determine the extent of infection. Thirty-seven patients had positive MRI for osteomyelitis and 19 were positive with conventional radiography. Thirteen patients had negative MRI healed with short course of antibiotics. Five patients with positive MRI received four weeks' course of intravenous antibiotics with two still having persistent infection in the six weeks follow-up. Thirty-two patients underwent surgery with favorable results. Sixty-two bone specimens were obtained for histologic evaluation of osteomyelitis. In cases with histologic proof of diagnosis, magnetic resonance sensitivity was 99%, specificity was 81%, and accuracy was 94%. Thus magnetic resonance imaging was shown to have a high sensitivity, specificity, and accuracy in detecting osteomyelitis.

Adult↗

Clinical experience with sotalol in patients with drug-refractory ventricular arrhythmias.

Sixty-five patients with symptomatic, drug-refractory, sustained ventricular tachycardia or fibrillation were treated with oral sotalol (80 to 480 mg twice daily). Sotalol was withdrawn in 11 patients because of continued inducibility of ventricular tachycardia at the time of follow-up electrophysiologic study. Therefore, the clinical effectiveness of sotalol could be evaluated in 54 patients followed up for 11.5 +/- 6 months (range 0.2 to 25). The actuarial incidence of successful sotalol therapy was 54 +/- 13% at 6 months and 47 +/- 13% at 12 months. In 39 patients who underwent electrophysiologic testing while receiving oral sotalol, the drug prevented the reinduction of ventricular tachycardia/fibrillation in 8 (20%). During follow-up study, arrhythmia recurred in 1 (17%) of 6 patients whose ventricular tachycardia was noninducible with oral sotalol and in 8 (44%) of 18 with inducible tachycardia but who were continued on oral sotalol therapy. Adverse effects were noted in 28 patients (42%), requiring drug withdrawal in 13 (22%) and dose reduction after hospital discharge in 10 (15%). Exacerbation of ventricular arrhythmia occurred in six patients (9%), one of whom had associated hypokalemia. Sotalol is frequently useful in the control of intractable, life-threatening ventricular arrhythmias, and its efficacy appears to be predicted by programmed stimulation. However, there is a high rate of limiting side effects, which precludes its use in a large number of patients, and a substantial risk of arrhythmia exacerbation.

Administration, Oral↗

The effect of selenium supplementation on immunity, and the establishment of an experimental Haemonchus contortus infection, in weaner merino sheep fed a low selenium diet.

Immunity in 12 weaner Merino sheep fed a low selenium (Se) diet (low Se sheep) was compared with that in 10 matching sheep fed the same diet but each given an intraruminal Se pellet (high Se sheep), while the sheep were housed in individual, sheltered pens. All sheep were challenged with killed Brucella abortus cells (days 0 and 28), rabbit red blood cells (days 0, 7 and 28) and corynebacterium pseudotuberculosis toxoid (days 0 and 28), and serum antibody titres were measured weekly for 8 weeks from day 0. The sheep were then experimentally infected with Haemonchus contortus, and slaughtered 8 weeks later. The mean antibody titre to B. abortus, measured by 4 different tests, was significantly higher in the high Se sheep on occasions during the primary immune response phase (Rose Bengal test - day 21 (p less than 0.05), day 28 (p less than 0.025); complement fixation - day 7 (p less than 0.05); enzyme-linked immunosorbent assay - day 14 (p less than 0.01); serum agglutination - no differences), but not during the secondary phase. The mean antibody titre to rabbit red blood cells, measured by haemagglutination test, was marginally higher in the high Se sheep on day 49 (p = 0.049). The mean antibody titre to C. pseudotuberculosis, measured by enzyme-linked immunosorbent assay, was not significantly different between the groups at any time during the trial. In addition, the mean in-vitro responsiveness of peripheral blood lymphocytes to stimulation with phytohaemagglutinin in the high Se sheep was significantly greater than that in 10 sheep from the low Se group on day 22 (p less than 0.01), but not day 50.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Conditioned taste aversion and conditioned drinking: two independent and opposing effects of 5-hydroxytryptophan?

Four experiments were carried out to examine the effects of 5-HTP in a conditioned taste aversion (CTA) paradigm. Using two-choice tests to measure the CTA, administration of 5-HTP following consumption of a novel flavour caused aversions to saline and saccharin solutions. In single-choice tests 5-HTP reduced consumption of saccharin, sugar cubes and beef-flavoured stock cubes, but only reduced saline consumption if animals had been pretreated with the 5-HTP decarboxylase inhibitor benserazide or the 5-HT receptor antagonist xylamidine, both of which act peripherally. Benserazide did not attenuate the CTA in any experiment. The results are interpreted in terms of two competing behavioural effects of 5-HTP: a centrally-mediated CTA and a peripherally-mediated conditioned drinking response.

5-Hydroxytryptophan↗

Specific disruption of spatial behaviour in rats by central muscarinic receptor blockade.

Three groups of rats were required to locate a single water bottle from an octagonal array of eight otherwise empty bottles. For one group (place navigation) the goal bottle remained in the same place from trial to trial; for a second group (cue navigation) the position of the goal bottle was cued by a black card over the nozzle; for the third group the goal bottle was uncued and moved randomly from trial to trial. Place and cue groups improved more than controls on all measures of performance. Scopolamine (0.2 mg/kg) substantially impaired performance in the place group, but had no effect on either of the other groups; the peripherally acting anticholinergic drug meth-scopolamine (0.2 mg/kg) had no effect in any group. In a second experiment, using food rewards, scopolamine caused a dose-dependent impairment of place navigation at doses from 0.025 to 0.4 mg/kg; 0.4 mg/kg also impaired cue navigation, but at this dose behaviour was visibly abnormal. In both experiments, scopolamine primarily affected speed of performance rather than accuracy. Olfactory cues were shown not to contribute to performance in either group. The results implicate central cholinergic transmission in the processing of visuo-spatial information.

Animals↗

A review of the sheep-multiple sclerosis connection.

This paper reviews a notion that the prevalence of multiple sclerosis is high in global areas where sheep populations are concentrated. Pilot studies are reported to serum antibodies in humans to three sheep diseases; focal symmetrical encephalomalacia (FSE), maedi visna and sarcocystis. In MS patients and controls antibodies were not found to the epsilon neurotoxin of the FSE organism, Clostridium welchii type D and to a caprine retrovirus that is closely related to maedi-visna virus. However, 34% of MS and control patients had antibodies to the protozoan parasite Sarcocystis spp., tissue cysts of which contain a powerful neurotoxin, sarcocystin. It is suggested that epidemiological MS prevalence rates for country areas of southern Australia require further study along with an examination for the prevalence of MS in vegetarians.

Adult↗

Protection of recently shorn sheep against adverse weather using plastic coats.

Sheep cold stressed for 10.5 h had plastic coats applied then the cold stress was continued. In 9 of 10 sheep (test group) showing hypothermia at the time coats were applied, body temperatures had returned to near normal 2.5 h later and to normal in 13.5 h. One sheep severely hypothermic before the coat was applied did not improve and was killed after 2.5 h. Sheep that were cold stressed without coats (wet controls) developed marked hypothermia and were killed between 10.5 h and 21 h. Rectal temperatures remained normal in controls that were cold stressed with coats on (coated wet controls) and in the controls not subjected to wetting (dry controls). Plasma cortisol increased markedly in the cold stressed sheep until plastic coats were applied, but the levels had fallen to normal levels 20 h later. Serum thyroxine levels increased at a faster rate in the test group and in wet controls than in the dry controls and coated wet controls during the first 9 h of cold stress. In 4 sheep of the test group energy utilisation increased markedly and remained high for a variable time after coats were applied then gradually returned to pre-cold stress levels. Liver tyrosine aminotransferase levels of the wet controls were markedly elevated compared to levels found in the test group sheep killed 79.5 h after coats were applied. Histological changes in the spleen and liver of wet controls was absent or only mildly present in the test group sheep. There was severe depletion of muscle and liver glycogen in the wet controls compared with the test group sheep, which were similar to the dry controls and coated wet controls.

Animals↗