Future of veterinary education.
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Biomedical subjects
Publications and source records attributed to D Taylor.
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We have evaluated two novel enzyme-linked immunosorbent assays (ELISAs) used to quantitate cyclic AMP. In one assay ELISA plates are coated with antigen consisting of a cyclic AMP-polylysine conjugate. Cyclic AMP samples added to plates are quantified by their ability to decrease the binding and anti-cyclic AMP antibodies to the coated antigen. A second ELISA utilizes a plated anti-immunoglobin technique in which plates are coated first with anti-goat IgG and then with goat anti-cyclic AMP antiserum. Cyclic AMP samples are quantified by their ability to compete with cyclic AMP-peroxidase conjugates for binding to the plated anti-cyclic AMP antibodies. The plated anti-immunoglobin ELISA proved to be somewhat more sensitive than the plated antigen ELISA and was comparable in sensitivity to an automated RIA for measuring cyclic AMP in standards and urine samples. Our data fit with the generalization that optimal ELISA sensitivity is obtained through the use of plated anti-immunoglobins rather than plated antigens. Further they demonstrate the practicality of utilizing small ligand-enzyme conjugates for ELISAs.
Using X-linked clonal analysis, mechanism of action of all-trans retinoic acid (ATRA) was sought in a 16-year-old female with relapsed clonally evolved acute promyelocytic leukemia (APL), who achieved complete remission. On ATRA, metamorphosis of peripheral blood leukemic promyelocytes to mature neutrophils was observed, despite the persistence of t(15;17) in 100% of bone marrow metaphases. DNA was extracted from fractionated serial blood specimens, collected at diagnosis, in first complete remission (CR), relapse, and during ATRA treatment. Using a phosphoglycerokinase (PGK) probe, the patient was heterozygous for both Bgl I and Bst XI PGK polymorphisms. Methylation analysis showed monoclonal leukemic promyelocytes with a polyclonal first CR achieved by standard chemotherapy. Subsequent examination, in relapse, of granulocytes appearing during ATRA treatment showed these to be monoclonal, proving these were derived from the neoplastic clone. The X-linked clonal analysis methodology has provided in vivo evidence of cellular differentiation as the mechanism of action of ATRA. Parallel studies of cytogenetic and clonal analysis showed a regression of the t(15;17) cytogenetic abnormality and return of a polyclonal PGK methylation pattern in 5 weeks, indicating a repopulation of marrow by normal stem cells. As standard cytogenetic techniques are inappropriate for nondividing cells, X-linked clonal analysis provides a marker system to allow insight into mechanism of drug action in malignant hematologic disease.
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Vitellogenin (Vg) concentrations in the hemolymph and ovarian development were studied in Ornithodoros moubata after treatment with precocenes 1 (P1) and 2 (P2). Precocene was dissolved in acetone or DMSO and topically applied to the dorsal surface of ticks: (1) at adult ecdysis; (2) 24 h before engorgement; (3) immediately after engorgement; and (4) 24 h after engorgement. Subsequently, P1 and P2 were dissolved in olive oil and injected through the gonopore into the body cavity 24 h after engorgement. Vitellogenin concentration was measured on days 5 and 10 after engorgement and ovarian development was scored on day 10, 20 or 30. Oviposition was also recorded and the average weight of eggs laid by females was determined. No differences in concentration of Vg in the hemolymph occurred between the control ticks and ticks treated topically or by injection with P1 and P2. Precocene did not suppress the synthesis of Vg in O. moubata. However, oviposition was reduced in ticks that survived repeated treatment with high doses of P2 dissolved in acetone.
Three cases are reported where continuous lumbosacral block was performed using a catheter through an epidural needle technique. Good unilateral lower limb surgical anaesthesia was achieved in all three cases with successful blockade of the lumbar and sacral plexuses. A 17-gauge Tuohy needle was positioned between the transverse processes of L4 and L5 and an epidural catheter inserted into the space between the quadratus lumborum and psoas muscles. Forty to seventy millilitres of local anaesthetic were injected and resulted in good surgical anaesthesia within 12-20 min. Radiographic studies in these patients confirmed placement of the catheter in close proximity to the lumbosacral plexus. Experience in a further 12 cases is also reported. There were no side-effects. The technique is successful and is recommended when unilateral lower limb anaesthetic is required and when spinal and epidural anaesthesia are contraindicated.
A method for the prediction of the time-course of bone adaptation based on an alternative hypothesis of strength optimization has been previously investigated and developed by Prendergast and Taylor. This paper extends our work in the study of the effectiveness of this bone adaptation model in predicting similar bone remodelling to that observed in animal experiments. In particular the experimental work which has been modelled is that of Lanyon, Goodship, Pye and McFie. An anatomical finite element model of the sheep's forelimb has been generated for this purpose and is used to estimate stresses in the bone structure for the normal and osteotomized condition. The propensity for remodelling of the altered bone structure is predicted using the proposed remodelling law for the new stress field in the bone structure. The preliminary results indicate an initial bone adaptation pattern similar to that observed experimentally without the necessity to use arbitrarily different constants for the endosteal and periosteal surfaces. We therefore suggest that the remodelling law based on damage and repair gives a better predictive model of bone adaptation than previous models.
The adaptation of bone around intramedullary fixated prostheses, such as the femoral component of the hip joint or the radial component of the elbow joint, is well documented in follow-up studies. Bone adaptation takes the form of proximal bone atrophy accompanied, in some cases, by distal bone hypertrophy. A mechanistic model has been formulated to predict bone adaptation based on the concept that the continuous processes of damage and repair regulate bone adaptation. We apply the model to investigate the significance of two features of intramedullary prosthesis design on bone adaptation: prosthesis Young's modulus and the presence of a prosthesis collar. Results, as well, as indicating some characteristics of accumulative-damage stimulated bone adaptation, predict that a low Young's modules stem will very much reduce the extent of bone loss whereas the presence of a collar will have no significant effect. The results predict that a collarless low stiffness prosthesis is one possible approach for improving the secondary stability of intramedullary-fixated orthopaedic implants.
BACKGROUND: Alport syndrome is an X-linked disease affecting basement membrane collagen. It is characterized by nephritis associated with high-tone sensorineural hearing impairment and ophthalmic signs. Although ocular changes have been described in adults, few data exist regarding the incidence of abnormal ocular features in adolescence and childhood. METHODS: Fifteen male and five female patients with Alport syndrome underwent ophthalmologic, audiologic, and nephrologic assessments. All patients studied had hematuria and a positive family history of Alport syndrome. Thirteen patients had a renal biopsy that showed characteristic electron microscopic changes of the disease. Eleven patients had high-tone sensorineural impairment. Electrophysiologic investigations performed included electroretinography, visual-evoked potentials, and electro-oculography. RESULTS: Two patients had early signs of anterior lenticonus, three had flecks in the retina, and two patients also had posterior subcapsular cataracts. None of the patients had significant electrophysiologic abnormalities. CONCLUSION: These findings indicate that ocular changes are uncommon and subtle in young patients with Alport syndrome, and suggest that the signs increase in frequency and severity with age.
There has been a traditional reluctance to remove a subluxed (ectopic) lens because of the high surgical risk. The use of closed intraocular microsurgical techniques, however, now allows greater intraoperative control with few complications. The authors present the results of subluxed lens extraction, by limbal or pars plana lensectomy, in 44 eyes of 24 patients, in which the indication for surgery was lens subluxation causing a reduction in visual acuity or uncorrectable refractive error. Visual acuity was improved in all cases after surgery, with no significant complications. Patients with reduced visual acuity secondary to ectopic lenses have a good visual prognosis after lensectomy using a closed intraocular microsurgical technique.
The life cycle of Gnathostoma nipponicum was examined by field survey and by experimental infection of animals with the larvae. Naturally infected larval G. nipponicum were found in loaches, catfish, and snakes. Experimentally, loaches, killifishes, frogs, salamanders, mice, and rats were successfully infected with the early third-stage larvae of G. nipponicum obtained from copepods (the first intermediate host), whereas snakes, quails, and weasels were not. Frogs, snakes, quails, and rats were experimentally infected with the advanced third-stage larvae (AdL3) from loaches. These results reveal that some species of fishes, amphibians and mammals can act as the second intermediate host and that some species of reptiles, birds and mammals can act as a paratenic host. The life cycle was completed in weasels, the definitive host, which were infected with AdL3 from loaches and started to evacuate eggs of G. nipponicun in faeces on days 65-90 postinfection.
We review the epidemiology, aetiology, pathogenetic mechanisms and clinical management of neonatal cataract. Visual development and the effects of visual deprivation in the infant with congenital cataract are discussed and related to the timing of surgery. Surgical techniques and the important operative and post-operative complications are discussed. We review post-operative management and compare the different techniques available for aphakic correction, and describe the VEP changes found in patients with monocular cataract.
When inoculated subcutaneously, the infective larvae of L. sigmodontis undergo complete development and produce a patent microfilaraemia in mice of the BALB background (BALB/c, BALB/K and BALB/B, with respectively the H-2d, H-2k et H-2b haplotypes). The most susceptible strain is BALB/c with all mice harbouring adult filariae and 47% of mice presenting with a patent microfilaraemia. Mice with the B10 background (B10, B10Br and B10D2, with respectively the H-2b, H-2k et H-2d haplotypes) are almost completely resistant to infection. Adult filariae were recovered from all mice of the CBA/Ca, CBA/HN, C3H/HeN, DBA/2N strains. However, the site and structural development of the parasite varied in each strain. Absence of microfilaraemia is associated with absent or abnormal spicules, reduced number of female filariae and small size of female filariae. These results show that the Major Histocompatibility Complex only modulates the developmental pattern of filariae within the limits imposed by background genes. Male CBA/HN and C3H/HeN were more susceptible to infection than female mice. Inverse phenomenon was observed with strains BALB/c; and, no host sex effect was seen in DBA/D2N.
Studies of development and behaviour from shortly after birth up to the age of 7 years are reviewed. Maternal alcohol consumption above 150-200 g/week is related to behaviour in many studies, but below this level there is little epidemiological evidence of association. There is no evidence that the levels of consumption associated with adverse behaviour are lower than those associated with adverse pregnancy outcome.
Electroretinography (ERG), especially when combined with visual evoked potential recording, can provide valuable information to the pediatric clinician assessing a young child with nystagmus who appears not to see. ERG changes are described in clinical conditions affecting rod and/or cone function, vitreoretinal disease, maculopathies, and disorders involving the retina and central nervous system. The role of ERG in monitoring treatment, and in excluding retinal disease prior to eye surgery, is also covered.
Adequate immunosuppression remains a major obstacle to successful xenotransplantation, with early xenograft rejection appearing to be mediated by humoral factors. Total-lymphoid irradiation (TLI) and 15-deoxyspergualin (DOSP) have been shown to be effective immunosuppressive agents in allografs. In this study, TLI alone and in combination with DOSP and cyclosporine were evaluated in the hamster-to-rat heterotopic cardiac xenograft model. The animals were divided into four groups: group 1--control (n = 9); group 2--TLI alone, administered pretransplant at 125 cGy/day, four days per week, for three weeks (n = 12); group 3--TLI plus CsA at 10 mg/kg/day (n = 17); and group 4--TLI plus DOSP at 2.5 mg/kg/day (n = 10). Tissue sections were taken from rejected xenografts in all treatment groups for histological examination. Complement-dependent cytotoxicity assays were performed on the control group and also the TLI-DOSP group. The control animals were found to have a mean graft survival of 3.2 +/- 0.4 days. TLI alone (5.8 +/- 0.7 days) did not significantly improve graft survival in comparison with the control group. Combination of TLI with DOSP (26.3 +/- 5.9 days) results in significantly improved survival (P less than 0.05) in comparison with the control, TLI alone, and combination of TLI and CsA (13.6 +/- 8.6 days). Complement-dependent cytotoxicity assays revealed that control groups have low rat antihamster lymphocytotoxic antibody titer (1/1-1/10) prior to xenografting, and that these antibody titers show a precipitous rise to a level of 1/640-1/1280 by day 3, the time at which rejection occurred. This correlates with the histological findings of the rejected hearts showing a severe humoral type of rejection and no evidence of cellular rejection. In contrast, animals in the TLI-DOSP group had markedly lowered rat antihamster lymphocytotoxic antibody titers (1/20-1/40) on day 3, and these titers only increased to 1/160 at time of rejection. This correlates with the histological findings of a lesser degree of humoral rejection in the TLI-DOSP group. Combination therapy with TLI and DOSP results in a marked increase of survival in xenografts in this model not seen with any other drug combination studied in over 500 xenografts in our laboratory. This study indicates that TLI combined with DOSP results in prolonged suppression of the antixenograft antibody response. This combination of agents appears to have the potential to prevent early xenograft rejection.
The effect of zinc and erythromycin on cultures inoculated with mixtures of different ratios of erythromycin sensitive (ES) and resistant (ER) Propionibacterium acnes cells was studied in vitro. Propionibacterium acnes ES outgrew P. acnes ER in the absence of erythromycin and zinc. At low levels of erythromycin ES outgrew ER, whilst the addition of 600 pg/ml zinc further reduced the growth of ER compared to ES. Growth of ER and ES were similar at levels of erythromycin near the minimum inhibitory concentration (MIC) of ES cells. Concentrations above the MIC for ES cells inhibited ES but not ER cells. At the higher concentrations of erythromycin, the addition of 96 ng/ml zinc delayed the growth of ER cells, whilst the addition of 300 micrograms/ml zinc prevented the growth of ER cells. The combination of erythromycin and zinc, at appropriate concentrations, inhibits both ES and ER.
Micrococcus sedentarius, an organism associated with pitted keratolysis, produced two proteinases in culture supernatant fluids, as shown by non-denaturing PAGE with overlaying with a casein substrate. A mixture had optimal activity at pH 10 with azocasein substrate. At pH 7.1 and 8.1 in continuous culture with varying dilution rates high proteinase production occurred at relative specific growth rates (mu rels) 0.39 and 0.77 and biomass concentrations decreased with increasing dilution rate. One proteinase was constitutive and varied little in production with different growth rates. The other proteinase was under control with high production at low growth rates and no production at high growth rates. With varying pH at mu rels 0.39 and 0.77 maximum biomass concentration and proteinase production occurred between pH 8.0 and 9.0 as did the highest specific growth rate. These results support the hypothesis that Mic. sedentarius produces pitting in the stratum corneum when the skin is hydrated and the pH rises above neutrality.