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Biomedical subjects

D L Hughes

Publications and source records attributed to D L Hughes.

At least 37 records · Page 2Linked to original sources

Two approaches to the facilitation of grammar in children with language impairment: an experimental evaluation.

Two approaches to grammar facilitation in preschool-age children with language impairment were evaluated. One approach was administered by a speech-language pathologist and the other was presented by the subjects' parents, who were trained by the speech-language pathologist. Both treatment packages ran for 4 1/2 months and made use of focused stimulation procedures and a cyclical goal-attack strategy. Subjects were 30 children between the ages of 3:8 and 5:10 (years:months) who had marked delays in grammatical development. Children who served in a delayed-treatment control group averaged no gains over their no-treatment period. In contrast, large treatment effects were observed for both treatment groups on three of four measures of grammatical expression. However, closer inspection of the data revealed that the effects for the clinician treatment were more consistent across treatment administrations than were those for the parent treatment. Although the specific contributions of the focused stimulation procedures and the cyclical goal attack strategy were not evaluated, the results support the viability of these components as parts of larger treatment packages. The results also support the participation of parents as primary intervention agents in grammar facilitation programs. When parents take such a large role in the intervention process, however, it is imperative that the children's progress be monitored carefully and that program adjustments be made whenever gains are smaller than expected.

Child↗

Family physicians' attitudes toward advance directives.

OBJECTIVE: To examine the attitudes toward, the experience with and the knowledge of advance directives of family physicians in Ontario. DESIGN: Cross-sectional survey. PARTICIPANTS: A questionnaire was mailed to 1000 family physicians, representing a random sample of one-third of the active members of the Ontario College of Family Physicians; 643 (64%) responded. RESULTS: In all, 86% of the physicians favoured the use of advance directives, but only 19% had ever discussed them with more than 10 patients. Most of the physicians agreed with statements supporting the use of advance directives and disagreed with statements opposing their use. Of the respondents 80% reported that they had never used a directive in managing an incompetent patient. Of the physicians who responded that they had such experience, over half said that they had not always followed the directions contained in the directive. The proportions of physicians who responded that certain patient groups should be offered the opportunity to complete an advance directive were 96% for terminally ill patients, 95% for chronically ill patients, 85% for people with human immunodeficiency virus infection, 77% for people over 65 years of age, 43% for all adults, 40% for people admitted to hospital on an elective basis and 33% for people admitted on an emergency basis. The proportions of physicians who felt that the following strategies would encourage them to offer advance directives to their patients were 92% for public education, 90% for professional education, 89% for legislation protecting physicians against liability when following a directive, 80% for legislation supporting the use of directives, 79% for hospital policy supporting the use of directives, 73% for reimbursement for time spent discussing directives with patients and 64% for hospital policy requiring that all patients be routinely offered the opportunity to complete a directive at the time of admission. CONCLUSIONS: Family physicians favour advance directives but use them infrequently. Most physicians support offering them to terminally or chronically ill patients but not to all patients at the time of admission to hospital. Although governments emphasize legislation, most physicians believe that public and professional education programs would be at least as likely as legislation to encourage them to offer advance directives to their patients.

Adult↗

Comparative evaluation of the neuromuscular and cardiovascular effects of pipecuronium, pancuronium, atracurium, and vecuronium under isoflurane anesthesia.

The neuromuscular and cardiovascular effects of intubating doses of pipecuronium 80 micrograms/kg, pancuronium 100 micrograms/kg, atracurium 500 micrograms/kg, and vecuronium 100 micrograms/kg were compared in 62 patients under isoflurane (end-tidal concentration = 0.5-1%) anesthesia. Pipecuronium, pancuronium, and vecuronium had no significant effect on systolic or diastolic blood pressure. In one patient the administration of atracurium resulted in significant hypotension. Heart rate was significantly increased only after the administration of pancuronium. The neuromuscular-blocking effect of pipecuronium and pancuronium appears to be twice as long as that of vecuronium and atracurium. Administration of neostigmine resulted in significantly faster recovery of muscle function in patients receiving vecuronium or atracurium. Although pipecuronium's neuromuscular-blocking effect is similar to that of pancuronium, its lack of cardiovascular effects more closely resembles that of vecuronium.

Adolescent↗

Studies on heterologous resistance between Schistosoma mansoni and Fasciola hepatica in inbred rats.

Fischer rats infected with Fasciola hepatica showed significant resistance to Schistosoma mansoni challenge, and vice versa, whereas immunization with 20 Krad-irradiated S. mansoni cercariae failed to protect against F. hepatica challenge, but did protect against homologous challenge. When groups of rats received intraperitoneal implants of newly excysted juvenile flukes, 20- to 22-day-old juveniles, or 8- to 10-week-old flukes, none was significantly protected against S. mansoni challenge, whereas juvenile implants did protect against homologous F. hepatica challenge. In passive transfer experiments in rats, serum from F. hepatica-infected rats or rabbits protected recipients against homologous, but not heterologous challenge, and serum from rats vaccinated with 20 Krad-irradiated S. mansoni cercariae protected recipients against homologous, but not heterologous challenge. These experiments provide evidence that the mechanisms involved in homologous and heterologous resistance are different, the latter lacking immunological specificity. Microsphere injections in F. hepatica-infected rats demonstrated 'shunting' from the portal system to the systemic circulation. If migrating schistosomula are also 'shunted' in Fasciola-infected rats, this, rather than immunologically specific effector mechanisms, might explain their failure to establish in the portal system.

Animals↗

Fasciola hepatica: site of resistance to reinfection in cattle.

The effective site of resistance to reinfection of cattle with Fasciola hepatica was examined by recovery of challenge flukes from either the liver or body cavity. Calves infected 18 or 26 weeks previously with F. hepatica showed levels of resistance to reinfection of 56 and 94%, respectively, as assessed by recovery of flukes from the liver 15-16 weeks after challenge. Plasma glutamate dehydrogenase (EC 1.4.1.3; GLDH) enzyme activity estimations revealed only a marginal increase in these latter resistant calves compared with previously naive controls, indicating minimal liver damage as a result of migrating flukes. By comparison, when immature challenge flukes were recovered from the body cavity 4 or 14 days after infection of corresponding previously infected or naive calves, there was no significant difference in numbers. It appears, therefore, that, in cattle, resistance mechanisms are effective against challenge flukes at or soon after penetration of the liver.

Animals↗

Early migration of immature Fasciola hepatica and associated liver pathology in cattle.

Immature Fasciola hepatica were successfully recovered from the body cavity of cattle from two to 21 days after oral infection. Flukes had penetrated the liver in large numbers by day 7 but there did not appear to be a corresponding reduction in the numbers recovered from the body cavity. Liver pathology showed a typical progressive tissue disruption with a neutrophil and lymphocyte infiltration by day 7 and a marked eosinophil response from day 14. The mesothelium of the liver capsule underwent metaplasia, becoming ultimately highly active and columnar.

Animals↗

Mapping of the S' subsites of porcine pancreatic and human leucocyte elastases.

Trifluoroacetyl dipeptide anilides have been synthesized and used to map the S' subsites of porcine pancreatic elastase and human leucocyte elastase. A confident mapping of these subsites, at least for the porcine enzyme, was possible since the x-ray crystallographic study of its complex with CF3CO-Lys-Ala-NH-Ph-p-CF3 at a resolution of 2.5 A (Hughes, D. L., Sieker, L. C., Bieth, J., and Dimicoli, J. L. (1982) J. Mol. Biol. 162, 645-658) shows the CF3CO group at the S1 subsite and the dipeptide anilide bound at sites close to the S'1-S'3 subsites. Furthermore the effect of substitution was easy to investigate since these ligands are reversible competitive inhibitors of elastases, whose mode of binding to the porcine enzyme has been shown by nuclear magnetic resonance spectroscopy (Dimicoli, J. L., Renaud, A., and Bieth, J. (1980) Eur. J. Biochem. 107, 423-432) to be essentially unique and common to all CF3CO peptide anilides. The total number of S' subsites was found to be three for both enzymes. The individual subsites have the following specificities: subsite S'1, in porcine pancreatic elastase this subsite prefers Lys to Ala or Glu. In human leucocyte elastase this subsite is less specific; subsite S'2, in porcine pancreatic elastase, this subsite has a marked specificity for Ala. It accommodates bulkier residues with some difficulty. In human leucocyte elastase there is a remarkable specificity for Leu at this subsite; subsite S'3, in porcine pancreatic elastase, this subsite has a high aromatic specificity. In human leucocyte elastase there is no such affinity in S'3 but favorable local interaction exists. These specificities are examined on the basis of the coordinates of the CF3CO-Lys-Ala-NH-Ph-p-CF3 . porcine pancreatic elastase complex. Furthermore the different specificities of the S'2 subsite found in our own work and proposed by Atlas (Atlas, D. (1975) J. Mol. Biol. 93, 39-53) are briefly discussed.

Anilides↗

Fasciola hepatica: migration of newly excysted juveniles in resistant rats.

Using transmission and scanning electron microscopy, the early migration of juvenile Fasciola hepatica was examined in naive and resistant rats. In naive rats, the migration of flukes to the peritoneal cavity was uneventful. In resistant rats, flukes were rapidly coated with antibody whilst still in the gut lumen and a proportion of the flukes were unable to penetrate the intestinal wall. Those that did penetrate were unharmed as they crossed the gut wall, but on entering the peritoneal cavity they were coated with antibody and host cells including eosinophils, neutrophils, macrophages, and mast cells. Eosinophils were seen degranulating onto the fluke surface, and this appeared to result in the erosion of the tegumental syncytium.

Animals↗

Fasciola hepatica: development of the tegument of normal and gamma-irradiated flukes during infection in rats and mice.

Rats and mice were infected with either normal metacercariae or metacercariae gamma-irradiated at 3 krad. or 4 krad. Flukes were recovered at various times after infection and their teguments examined using a transmission electron microscope. In normal flukes, the secretory granules T0, T1 and T2 were all seen during tegumental development. The teguments of flukes from mice developed faster than the corresponding teguments in rats. T0 granules were present from day 0 to day 10 post-infection (p.i.) in mouse flukes and from day 0 to day 14 p.i. in rat flukes. T1 granules first appeared in mouse flukes by day 4 p.i. but not until day 8 p.i. in rat flukes. T2 granules were seen in mouse flukes 2 days p.i. but not before 6 days p.i. in rat flukes. gamma-Irradiation at 4 krad prevented normal tegumental development in flukes from both rats and mice. T0 granules were present at all times in flukes from either host. T1 granules were produced in mouse flukes but their appearance was delayed until day 6 p.i. No significant production of T2 granules occurred in flukes from either host. Parasite survival was also affected by gamma-irradiation and none of the flukes reached maturity. Flukes from rats died between 10 and 21 days p.i. and flukes from mice died between 14 and 28 days p.i. gamma-Irradiation of metacercariae at 3 krad. had an extremely variable effect on subsequent tegumental development in both rats and mice. Some flukes developed normally, some showed development associated with gamma-irradiation at 4 krad, whilst some showed intermediate development.

Animals↗

Bile flow, bile salt secretion and the excretion of iron, copper, zinc and manganese in the bile of calves infected with Fasciola hepatica.

The rate of flow of bile and the concentrations of iron, copper, zinc and manganese in bile were measured in four bull calves, before and for at least 23 weeks after infection with 1000 metacercariae of Fasciola hepatica. Bile flow rate began to increase about 10 weeks after infection and had increased nearly three-fold by 23 weeks but bile salt (total-cholate) secretion rate remained similar to that of two control calves. The excretion of iron in bile increased rapidly eight weeks after infection from a mean of 21.5 nmol per minute to reach 469 nmol per minute at 14 weeks and this increase was accompanied by an increase in gamma-glutamyl transpeptidase activity in plasma. 59Fe studies showed that most of the iron in the bile of infected calves was derived from red blood cells. There were no changes in the excretion of zinc, copper or manganese in bile which could be associated with the infection.

Animals↗