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Biomedical subjects

I D Duncan

Publications and source records attributed to I D Duncan.

At least 19 recordsLinked to original sources
PubMed1995

Gene expression and oligodendrocyte development in the myelin deficient rat.

The proteolipid proteins play a major role in the structure of the CNS myelin sheath, but they have also been implicated in the oligodendrocyte development leading to myelination. Mutations in the PLP gene result in severe dysmyelination and a paucity of mature oligodendrocytes. The myelin deficient (md) rat, carrying a Thr75-->Pro substitution present in both isoforms of proteolipid protein (PLP and DM20), is the most severely affected of the PLP mutants described to date. The expression of myelin associated genes was quantitated to determine the effect of the mutation on oligodendrocyte development in vivo. At 5 days postnatal, gene expression in the md rat approximated that in age-matched control rats, but as they matured, there was a progressive inhibition of gene expression in the md rats. The genes expressed late in the myelination program (PLP and MBP) were affected more dramatically than those expressed earlier in oligodendrocyte development (CNP and GPDH). The results indicate that the later stages of oligodendrocyte maturation and myelin elaboration are inhibited.

Animals↗
PubMed1995

Canine oligodendrocytes undergo morphological changes in response to basic fibroblast growth factor (bFGF) in vitro.

The mature oligodendrocyte, though able to divide under certain circumstances, has been regarded as incapable of changing into a phenotypically plastic cell type. To further explore this question, we developed an in vitro system in which a virtually pure population of early postnatal canine oligodendrocytes were cultured in a serum free, defined medium. We tested the oligodendrocytes' morphological and mitotic responses to concentration of basic Fibroblast Growth Factor (bFGF) ranging from 5 ng to 100 ng/ml. We found that bFGF effected both the morphology and mitotic potential of these cells. In addition, oligodendrocytes exposed to bFGF respond to 10% fetal bovine serum (FBS) by undergoing morphological changes that are quite different than naive oligodendrocytes exposed to 10% FBS, suggesting that bFGF causes some fundamental change in plasticity.

Animals↗
PubMed1995

Acute dispersion of glial cells following transplantation into the myelin-deficient rat spinal cord.

Evaluation of glial cell migration following transplantation can be difficult as the force of the injection itself may cause the cells to become immediately dispersed. In this study we evaluated the extent of spread of cells after injection of 1 microliter of a dissociated cell suspension (50,000 cells/microliter) into the dorsal columns of the thoracolumbar spinal cord in the neonatal myelin-deficient (md) rat. Spinal cords were examined at 0, 4, and 24 h after injection to determine the dispersion of cells away from the initial site of deposition. Examination of skip-serial sections collected at 50-microns intervals rostral and caudal to the site of transplantation showed that the injection could result in a spread of transplanted cells up to 1,600 microns. Migration should therefore be defined as the detection of cells beyond the rostral-caudal boundaries defined by the injection deposition. Cell dispersion should be taken into account when evaluating the results of migration in previous and future experiments concerning glial cell transplantation.

Animals↗
PubMed1995

Cold coagulation.

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Age Factors↗
PubMed1995

Screening for cervical neoplasia in Dundee and Angus: 10 years on.

OBJECTIVE: To evaluate the effect of changed cervical screening policies on a steady population with low migratory tendencies. DESIGN: A retrospective analysis study. SETTING: Dundee and Angus, Scotland. SUBJECTS: All women who developed cervical carcinoma between 1957 and 1992. MAIN OUTCOME MEASURES: The incidence of and mortality from cervical cancer after the introduction of organised cervical screening in 1962, according to age, stage, histology and screening history. RESULTS: The initial fall in incidence of cervical cancer seen in women between 35 and 54 years after the introduction of cervical screening was not sustained during the last 10 years of our study and appears to have been transferred to women aged 55 years and older instead. After 1976 an increase in the incidence of cervical cancer was seen in women under 35 years. The reduction in mortality from cervical cancer appears to have reached a plateau since 1976. No effect of cervical screening was seen on the incidence of adenocarcinoma of the cervix. CONCLUSIONS: The effect of changed cervical screening policies has been shown for a small population for a period of 35 years. The incidence of the higher stages of squamous cervical cancer continues to fall. The increase in incidence of cervical cancer in women under 35 years confirms similar trends seen in other countries. A background mortality rate refractory to further intensification of screening appears to have been reached. Adenocarcinoma of the cervix appears to gain in importance as cervical screening policies are shown to have their effect on its squamous counterpart.

Adenocarcinoma↗
PubMed1994

Transplantation of an oligodendrocyte cell line leading to extensive myelination.

Oligodendrocytes, the myelin-forming cells of the central nervous system, can be generated from progenitor cell lines and assayed for their myelinating properties after transplantation. A growth-factor-dependent cell line of rat oligodendrocyte progenitors (CG4) was carried through 31-48 passages before being transplanted into normal newborn rat brain or the spinal cord of newborn myelin-deficient (md) rats. In md rat spinal cord, CG4 oligodendrocyte progenitors migrated up to 7 mm along the dorsal columns, where they divided and myelinated numerous axons 2 weeks after grafting. CG4 cells were transfected with the bacterial lacZ gene and selected for high beta-galactosidase expression. The cell migration and fate of these LacZ+ cells were analyzed after transplantation. In normal newborn brain, LacZ+ oligodendrocyte progenitors migrated along axonal tracts from the site of injection and integrated in the forming white matter. In md rats, extensive migration (up to 12 mm) was revealed by staining for beta-galactosidase activity of the intact spinal cord where many grafted cells had moved into the posterior columns. Similar migration and integration of grafted cells occurred in the spinal cord of normal myelinated rats and after a noninvasive grafting procedure. Thus, oligodendrocyte progenitors can maintain their ability to migrate and myelinate axons in vivo after multiple passages in vitro. Such progenitor cell lines can be used to study the molecular mechanisms underlying oligodendrocyte development and the repair of myelin in dysmyelinating diseases.

Animals↗
PubMed1994

Transplantation of glial cells enhances action potential conduction of amyelinated spinal cord axons in the myelin-deficient rat.

A central issue in transplantation research is to determine how and when transplantation of neural tissue can influence the development and function of the mammalian central nervous system. Of particular interest is whether electrophysiological function in the traumatized or diseased mammalian central nervous system can be improved by the replacement of cellular elements that are missing or damaged. Although it is known that transplantation of neural tissue can lead to functional improvement in models of neurological disease characterized by neuronal loss, less is known about results of transplantation in disorders of myelin. We report here that transplantation of glial cells into the dorsal columns of neonatal myelin-deficient rat spinal cords leads to myelination and a 3-fold increase in conduction velocity. We also show that impulses can propagate into and out of the transplant region and that axons myelinated by transplanted cells do not have impaired frequency-response properties. These results demonstrate that myelination following central nervous system glial cell transplantation enhances action potential conduction in myelin-deficient axons, with conduction velocity approaching normal values.

Action Potentials↗
PubMed1994

Myelination by cryopreserved xenografts and allografts in the myelin-deficient rat.

This study examined the ability of freshly prepared and cryopreserved canine oligodendrocytes to myelinate axons following transplantation into the myelin deficient (md) rat. The effects of immunosuppression, and the age of the donor tissue, were also examined. Canine glial cells, dissociated from the spinal cords at E50, P2, P20, P28, and P50, were transplanted into the spinal cords of myelin-deficient rats as single cell suspensions. Both cryopreserved (E50 and P28) and freshly dissociated tissue (P2, P20, and P50) were able to form myelin within 13 days of transplantation. Cells from younger donors (< P20) myelinated more md axons than those from older donors. In those rats which received xenografts and which were treated with cyclosporin A there was markedly less cellular infiltration than in untreated animals. For comparison with these xenografts, fresh and cryopreserved adult rat glia were also transplanted. Eight days after transplantation, myelination by allografts of cryopreserved rat glia was qualitatively similar to that produced by freshly prepared cells. These results show that oligodendrocytes transplanted as xenografts are capable of myelinating rat axons, and that cryopreserved glia retain their capacity to myelinate in vivo.

Animals↗
PubMed1993

Axonal neurofilamentous accumulations: a comparison between human and canine giant axonal neuropathy and 2,5-HD neuropathy.

The neuropathy produced by the hexacarbon 2,5-hexanedione (2,5-HD) resembles human and canine inherited giant axonal neuropathy (GAN) in the presence of giant axonal swellings that contain accumulations of neurofilaments. The accumulations are both paranodal and internodal in GAN and 2,5-HD induced neuropathy. Detailed morphometry on the neurofilaments reveals that the changes in human and canine GAN are closely similar and differ from those of 2,5-HD neuropathy, suggesting that the mechanisms underlying the formation of the axonal neurofilamentous accumulations differ between the two conditions. In both human and canine GAN, the neurofilaments are more closely spaced and are of greater diameter than in 2,5-HD neuropathy. The changes in the NF in GAN may be the consequence of flattening of the side-arms of the neurofilaments against the axis of the filaments.

Animals↗
PubMed1993

The Royal College of Obstetricians and Gynaecologists micro-invasive carcinoma of the cervix study: preliminary results.

OBJECTIVES: To determine how micro-invasive carcinoma of the cervix is diagnosed and treated in the United Kingdom. To record the frequency of the various pathological features which comprise the histological diagnosis of micro-invasion, and to assess their relevance to outcome. DESIGN: Prospective observational study. SETTING: Hospitals throughout the United Kingdom. SUBJECTS: Two hundred and eighty-six cases were submitted for entry into the study. Following independent review of the histological material 116 cases were excluded: 41 were not accompanied by histological slides for review, 55 had no evidence of invasive disease, 17 had invasive disease greater than FIGO Stage 1a, and three were adenocarcinomas. The remaining 170 cases were registered for the study but follow up was incomplete in 18. This report concerns the 152 women with complete follow up to 1991. RESULTS: The age of the 152 women ranged from 22 to 65 years (median 36 years). In 116 women (76%) the diagnosis was made by cone biopsy (cold knife, loop diathermy, or laser) or wedge biopsy, in 9 women (6%) the diagnosis was made by hysterectomy, and in 27 women (18%) punch biopsy suggested an invasive lesion and subsequent excisional treatment (including radical hysterectomy with node dissection in three) demonstrated micro-invasion. The depth of invasion was up to 3 mm in 142 women (93%) and 3.1 to 5 mm in 10 women (7%). Capillary-like space involvement was present in 12 women (8%). Treatment methods used were local cervical surgery in 79 women (52%), simple hysterectomy in 63 (41%), and radical hysterectomy in 10 (7%). There was only one known recurrence and death due to cervical carcinoma. CONCLUSION: There is no uniformity in the management of micro-invasive carcinoma of the cervix. The frequency of recurrence, lymph metastases, and death is low. Nonradical surgery appears to give satisfactory results.

Adult↗
PubMed1993

The risks of symptomatic vaginal candidiasis after oral antibiotic therapy.

It is generally accepted that antibiotic use can result in vaginal fungal overgrowth, although evidence estimating the extent to which this causes symptomatic vaginitis is scant. In a study using the prescription of vaginal antifungal preparations as a surrogate measure of vaginal candidiasis, a cohort of women taking antibiotics had a higher incidence of vaginal candidiasis after antibiotic exposure than beforehand (relative risk 2.3; 95% confidence interval 1.9-3.0); this risk was highest in those aged 36-40 years (RR 6.0, 95% CI 2.9-12.5). The attributable risk was highest among those who were taking cephalosporins (AR 12.8%, 95% CI 9.1-16.5). In a case-control study, comparing previous antibiotic exposure among women using vaginal antifungal agents and matched controls, antibiotic exposure was higher among those using vaginal antifungal agents during the previous 28 days, with an odds ratio of 5.5 (95% CI 3.8-7.9).

Administration, Oral↗
PubMed1992

Randomised study of two doses of cisplatin with cyclophosphamide in epithelial ovarian cancer.

Cisplatin is generally accepted to be the most active cytotoxic agent for the treatment of ovarian cancer but the optimum dose remains unclear. We have performed a randomised trial to assess the importance of cisplatin dose in the treatment of advanced epithelial ovarian cancer. Patients were randomly assigned treatment with 50 mg/m2 (low dose) or 100 mg/m2 (high dose) cisplatin plus 750 mg/m2 cyclophosphamide, for a maximum of six cycles with intervals of 3 weeks. We planned to recruit 300 patients, but an interim analysis on the first 165 indicated a highly significant survival difference (p = 0.0008). Recruitment was therefore stopped and the trial patients were followed-up for 12 months longer. The relative progression rate (high-dose/low-dose) after 12 months' extra follow-up was 0.55 (95% confidence interval 0.37-0.81, p = 0.003) and the relative death rate 0.53 (0.34-0.81, p = 0.003). Overall median survival was 69 weeks in the low-dose group and 114 weeks in the high-dose group. Residual disease extent before chemotherapy had an important influence--patients with lesions of less than 2 cm did best; if given high-dose cisplatin their median survival was 3 years. 56 low-dose and 45 high-dose patients completed six cycles of chemotherapy; 15 and 9 patients, respectively, were withdrawn early because of progressive disease and treatment was stopped in 6 and 25, respectively, because of unacceptable side-effects or patient refusal. Toxic effects were significantly greater in the high-dose group, especially those on the nervous system and ears, alopecia, vomiting, and anaemia. Although the higher dose of cisplatin clearly leads to better results in terms of survival, its overall clinical benefit in the management of ovarian cancer will depend on further improvements in measures to alleviate toxic effects.

Adult↗
PubMed1992

Determination of the early age of onset of equine recurrent laryngeal neuropathy. 1. Muscle pathology.

The age of onset of equine recurrent laryngeal neuropathy has not been ascertained, although the clinical condition of left laryngeal hemiplegia ("roaring") has been recognized for centuries. The purpose of this study was to evaluate the laryngeal muscles of draft horse foals for the presence of fiber-type grouping, indicating denervation and reinnervation, and to determine if histological evidence of recurrent laryngeal neuropathy was present. Abductor and adductor laryngeal muscles from the left and right sides were collected immediately after euthanasia from male draft horse foals, six less than 2 weeks and four 6 months of age, and stained for myosin ATPase. A morphometric test was used to objectively evaluate several areas from each muscle for fiber-type grouping. Extensive fiber-type grouping which was characteristic of recurrent laryngeal neuropathy was found in one of the young foals and all of the older foals. Four of the young foals had some areas of fiber-type grouping suggestive of mild, early changes associated with recurrent laryngeal neuropathy. One of the young foals had no fiber-type grouping present in any of the laryngeal muscles evaluated. These findings suggest an early age of onset of recurrent laryngeal neuropathy.

Animals↗
PubMed1992

Determination of the early age of onset of equine recurrent laryngeal neuropathy. 2. Nerve pathology.

The left and right recurrent laryngeal nerves and peroneal nerves from two groups of foals, one less than 1 month of age and the other 6 months of age, were examined by light and electron microscopy. While there was no evidence of fiber loss on light microscopy, occasional onion bulbs, regenerating clusters and swollen axons were seen in the recurrent laryngeal nerves. To quantitate these changes, total counts of the main pathological structures were performed using the electron microscope. In all the foals the most common abnormality seen in the laryngeal nerves were Bungner bands, which were most numerous in the left recurrent laryngeal nerve of the older group of foals. Swollen axons which contained accumulations of organelles were seen in both age groups but were more common in the older foals. Likewise, onion bulbs were more frequent in the older animals but were also seen as well-formed structures in a foal less than 2 weeks of age. These findings confirm the previous report of neurogenic changes in the laryngeal muscles of foals and suggest that recurrent laryngeal neuropathy has an early and possible prenatal onset in the horse.

Animals↗
PubMed1992

The taiep rat: a myelin mutant with an associated oligodendrocyte microtubular defect.

This report describes a new inherited disorder of myelination in the rat, named taiep, in which failure of normal myelination of the CNS and subsequent demyelination result in a progressive neurological disturbance. At two months of age, myelin is present throughout the spinal cord, but is immature in the fasciculus gracilis and corticospinal tracts despite the presence of abundant oligodendrocytes. By 12 months, myelin has largely been lost in these spinal cord tracts and also in more rostral parts of the CNS, such as the cerebellum and optic nerves. Other funiculi of the spinal cord show a more diffuse lack of myelin. Oligodendrocytes develop a unique cellular abnormality, most obviously in older rats, which is characterized by the accumulation of microtubules throughout their cytoplasm. As the mutant rats age, there is a continued protracted breakdown of myelin throughout the CNS, with evidence suggesting either persistent hypomyelination or attempts at remyelination of affected axons. It is proposed that the microtubular defect in oligodendrocytes results in a disruption of the normal myelination process in certain areas of the CNS of this mutant, and eventually leads to failure of maintenance of the myelin sheath.

Animals↗
PubMed1992

A randomised study comparing standard dose carboplatin with chlorambucil and carboplatin in advanced ovarian cancer.

A total of 161 previously untreated patients with FIGO stage III or IV epithelial ovarian cancer were randomised after surgery to receive six courses of either carboplatin 400 mg m-2 alone (Arm A) or carboplatin 300 mg m-2 with chlorambucil 10 mg day-1 for 7 days (Arm B). The median progression free survival (PFS) was similar: arm A: 45 weeks; arm B: 61 weeks (P = 0.830). Multivariate Cox regression analysis showed that the extent of residual disease and performance status were the most important prognostic factors for PFS. Fifty-two per cent of patients received dose escalations based on nadir blood counts, and 89% of all dose adjustments were made according to protocol. Failure to achieve a significant degree of leucopenia was associated with worse progression free survival (P less than 0.001). A total of 29.4% of patients fall into this category. The median survival was similar in both arms, i.e. 75 weeks. It is unlikely that there is any major clinical advantage to adding chlorambucil to single agent carboplatin for the management of advanced ovarian cancer, but whether used in combination or a single agent, the dose of carboplatin should be sufficient to cause at least grade I leucopenia. This may best be achieved by determining the initial dose based on renal function, and then adjusting subsequent doses according to nadir blood counts.

Adult↗
PubMed1992

Functional capacities of transplanted cell-sorted adult oligodendrocytes.

Previous work has shown that transplanted dissociated glial cells derived from neonatal rats can myelinate areas of the myelin deficient (md) rat spinal cord. In the present studies we have examined the ability of adult glial cells, either as suspension of mixed glial cells or as 01 positive oligodendrocytes purified by cell sorting, to myelinate md rat axons following transplantation. Mixed glial cell preparations from adult rats myelinated large areas of either, dorsal, lateral or ventral columns. These areas contained clumped, transplanted oligodendrocytes. In addition, preparations containing over 90% 01 positive oligodendrocytes were also capable of myelinating large numbers of axons upon transplantation. These results suggest that adult oligodendrocytes may play an important role in remyelination of the adult CNS.

Animals↗