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Biomedical subjects

D Nicol

Publications and source records attributed to D Nicol.

At least 37 records · Page 2Linked to original sources
PubMed1997

Potential for bilateral nephrectomy to reduce oxalate release after combined liver and kidney transplantation for primary hyperoxaluria type 1.

Primary hyperoxaluria type 1 (PH-1) is frequently associated with end stage renal failure due to urinary calculi, obstructive uropathy and interstitial deposits of calcium oxalate. The currently accepted treatment for PH-1 is liver transplantation to replace the deficient enzyme peroxisomal alanine glycoxylate aminotransferase (AGT) and a simultaneous renal transplant to restore renal function. The transplanted kidney may become significantly impaired or fail when systemic calcium oxalate is eliminated by renal excretion. The native kidneys are a major source of this oxalate. This study was undertaken to determine whether there is a difference in oxalate clearance following combined liver-kidney transplant in patients with PH-1 by comparing the effect of native kidney nephrectomy at the time of transplantation against leaving the native kidneys in situ. Regression analysis was used to compare daily urinary oxalate excretion corrected for body surface area. There was a significant reduction in urinary oxalate excretion (P < 0.05) in the patient who had undergone bilateral nephrectomy compared to the patient whose native kidneys remained in situ for the first 100 d following combined liver and kidney transplantation. No difference was observed in the serum oxalate levels between patients over the same period or in the renal function assessed by creatinine clearance corrected for body surface area. Total body oxalate load was not determined in this study. A larger study should be undertaken to examine the benefits of nephrectomy in reducing oxalate deposition in recently inserted allografts for patients with PH-1.

Adult↗
PubMed1997

A prostate-specific antigen-like protein associated with renal cell carcinoma in women.

Renal cell carcinoma (RCC) is the most common form of cancer affecting the kidney. There is currently no biochemical marker for this disease. We have shown that serum-immunoreactive prostate-specific antigen (PSA) levels, as measured by the two-site Ciba-Corning ACS:180 immunochemiluminometric assay, are elevated in women with RCC. Although the levels were low (0.13-0.89 microgram/l), serum PSA was clearly measurable prior to surgery in 13 of 17 women (76%) with RCC. Significantly, the PSA levels fell to undetectable after nephrectomy. Seventeen normal women also had undetectable (<0. 1 microgram/l) PSA levels. Two women, who had several serum PSA measurements performed postoperatively, showed a t(1/2) of 2-3 days equivalent to that observed for PSA in men following radical prostatectomy for prostate cancer. The 17 RCCs evaluated in this study consisted of 10 stage A, 4 stage B, and 3 stage C tumors. There was no relationship between tumor size, stage, or serum-immunoreactive PSA level, although the majority of these tumors are low grade. We have shown by reverse transcription-PCR, using PCR primers directed to the NH2 terminal coding region of the KLK3 (PSA) gene and the closely related KLK1 and KLK2 genes, that these genes are not expressed in these tumors. Our findings show, however, that elevated levels of a circulating PSA-like protein are present in women with RCC.

Adult↗
PubMed1995

Geographic and microgeographic genetic differentiation in two aphid species over southern England using the multilocus (GATA)4 probe.

Samples of the grain aphid Sitobion avenae (F.) and the rose-grain aphid Metopolophium dirhodum (Walker) were collected in late March from wheat fields and adjacent road-side grasses at a number of locations in southern England. Unparasitized aphids were DNA fingerprinted using the multilocus (GATA)4 probe. Over all locations, the fingerprints of individual S. avenae caught in wheat had lower overall average distances of band migration (ADBM) and shared a higher proportion of bands, than fingerprints of individuals caught in adjacent road-side grasses. The ADBM of fingerprints of S. avenae collected on road-side grasses altered significantly with geographical location, while the ADBM of fingerprints of S. avenae caught on wheat did not. A comparison of the fingerprints of individual M. dirhodum caught in wheat and neighbouring road-side grasses did not reveal any genetic differentiation. Fingerprints of M. dirhodum that were caught in the same host type did however, show significant variation in ADBM between different locations. With both S. avenae and M. dirhodum, spatial autocorrelation revealed that locations that were close together were no more likely to have individuals with similar ADBM than locations that were far apart. Our results suggest that (i) particular clones of S. avenae prefer to colonize wheat, and/or that (ii) particular clones of S. avenae perform better on wheat than other clones. It is unclear why M. dirhodum did not show any genetic structuring according to host type, but this species appears to engage in sexual reproduction much more frequently than S. avenae in southern England.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Urological training in Australasia: perceptions of recent fellows and current trainees.

In this study we sought to determine the opinions of recent Fellows and current trainees on the state of urological training in Australasia. Self administered questionnaires were mailed to all urologists in Australia and New Zealand who had obtained their FRACS from 1988 to the present, as well as all current advanced urological trainees. Eight-seven per cent of Fellows and ninety-four per cent of trainees completed and returned the questionnaire. Most Fellows and trainees felt that their training adequately equipped them for subsequent independent practice. At the completion of training and FRACS examination the majority of respondents felt competent in dealing with most urological conditions. However, many did not feel confident with paediatric and specialized or complex adult urology, particularly oncology and reconstruction. Post-Fellowship training, however, appears valuable in overcoming these deficiencies. Several limitations were also noted as a consequence of the fact that training is based entirely in the public hospital system. This created particular difficulties with respect to outpatient or 'office' urology as well as exposure to some non-acute conditions such as urinary incontinence and infertility. The current research requirements of training do not appear to provide trainees with an adequate knowledge of scientific method, with many respondents not feeling equipped to critically appraise urological literature. High levels of competence are also not attained for other important professional skills, particularly communication with other medical practitioners. Despite its importance for learning, feedback on progress is not adequately provided and this was seen as a major problem with current urological training in Australasia. The majority of respondents felt that mentors required specific training to facilitate feedback to trainees.

Adult↗
PubMed1995

Nephrogenic metaplasia: long-term haemodialysis and anuria as potential risk factors and reversibility with renal transplantation.

AIM: To determine the incidence of nephrogenic metaplasia in patients with defunctionalized bladders due to long-term end-stage renal failure on haemodialysis. METHODS: From the dialysis registry of the Princess Alexandra Hospital 13 anuric patients who had been on haemodialysis for 10 or more years were identified. Of these, seven were currently awaiting renal transplantation and six had successful transplants. Endoscopic assessment of their lower urinary tracts was performed. RESULTS: Three cases of nephrogenic metaplasia were identified. In one case this led to significant haematuria following transplantation. However, the changes of nephrogenic metaplasia disappeared over the subsequent 18 months without specific treatment. CONCLUSIONS: It appears that a chronically defunctionalized bladder in the presence of end-stage renal failure is associated with an increased risk of nephrogenic metaplasia. These changes may spontaneously regress following transplantation and restoration of bladder function.

Anuria↗
PubMed1994

An analysis of secondary spread by putative clones of Sitobion avenae within a Hampshire wheat field using the multilocus (GATA)4 probe.

Grain aphids (Sitobion avenae (F.)) were collected from forty-four wheat ears in a Hampshire field at three times during the growing season. On each occasion, individual aphids were profiled using the multilocus (GATA)4 probe. During the full head emergence and full anthesis growth stages of wheat, each ear generally supported a genetically distinguishable aphid colony which consisted of genetically indistinguishable individuals (putative clones). This information strongly suggests that individual ears were colonized by single immigration events. By the late milky ripe stage, most ears supported two or more such clones. The total number of clones declined and the spatial separation of identical clones increased markedly over the duration of the study, which strongly suggests that secondary spread rather than increased immigration was responsible for the increased clonal diversity of ears. In addition, the profiles of individual S. avenae became more alike as the season progressed and samples became dominated by particular clones indicating either differential survival or reproduction among clones.

Animals↗
PubMed1994

Familial testicular carcinoma: in search of genetic triggers.

Two cases of testicular tumours in non-twin brothers of a cancer-prone family are described. Cytogenetic studies of these two patients and human leucocyte antigen (HLA) typing of the family failed to identify any genetic defects. The authors propose using linkage analysis for further genetic studies but would require additional families for this to be performed.

Adult↗
PubMed1994

Automated microbiological assay of thiamin in serum and red cells.

AIMS: To develop a sensitive, direct, automated method for the measurement of serum and red cell thiamin. METHODS: A microbiological assay using a chloramphenicol resistant strain of Lactobacillus fermenti as the test organism was developed. Addition of chloramphenicol and cycloheximide to the assay medium suppressed bacterial and yeast contamination and enabled tests to be automated without recourse to aseptic procedures. Evaluation of the assay included precision analysis and estimation of thiamin recovery. Results obtained on red cell extracts were compared with an established colorimetric (thiochrome) method. RESULTS: Acceptable intrabatch and interbatch precision was obtained and good recovery of thiamin added to serum was obtained. Non-parametric reference ranges based on the results from 505 healthy people were: serum thiamin 11.3-35.0 nmol/l and red cell thiamin 190-400 nmol/l. Results were not age or gender related. The method gave results for red cell thiamin which were significantly higher than those obtained with an established thiochrome method. CONCLUSIONS: This automated microbiological assay is sensitive to 2.0 nmol/l of thiamin and allows tests to be set up at the rate of 100 per hour and after 20-22 hours allows incubation results to be read at 60 per hour. The method has proved reliable, suitable for the assay of large numbers of samples, and relatively inexpensive to perform.

Colorimetry↗
PubMed1994

Effect of calcium-channel blockers on cyclosporine clearance and use in renal transplant patients.

OBJECTIVE: To determine the effect of calcium-channel blockers (CCBs) on cyclosporine dose, clearance, and cost, and their effect on kidney graft function and survival in patients who underwent kidney transplant. DESIGN: A total of 176 adults receiving 177 transplants were studied retrospectively. Patients were stratified as follows: no CCB (n = 57), diltiazem (n = 13), nifedipine (n = 37), and verapamil (n = 70). Patients received cyclosporine 3-4 mg/kg by continuous infusion for 5 days followed by cyclosporine 10 mg/kg/d po to maintain initial whole blood concentrations of 300-400 ng/mL. Clearance of intravenously administered cyclosporine was calculated following at least 48 hours of the same dose by continuous infusion. The amount and cost of cyclosporine used during the first 10 days of oral therapy were also calculated. RESULTS: Patients receiving diltiazem, but not verapamil or nifedipine, had decreased clearance of intravenously administered cyclosporine compared with that of the mean control group. The mean clearance of intravenously administered cyclosporine +/- SD in patients receiving no CCB was 5.1 +/- 1.5 mL/min/kg, diltiazem was 3.7 +/- 0.8 mL/min/kg, nifedipine was 6.4 +/- 1.9 mL/min/kg, and verapamil was 5.2 +/- 2.2 mL/min/kg. The amount and cost of 10 days of oral cyclosporine therapy was decreased in the verapamil group (5.7 +/- 1.5 g and $257 +/- 69) compared with that of the control group (6.7 +/- 1.6 g and $304 +/- 72) (p < 0.001). There was no significant difference among the groups with respect to immediate graft function, 1-year serum creatinine concentration, or 1-year graft survival. CONCLUSIONS: Diltiazem decreased the clearance of intravenously administered cyclosporine. Although verapamil did not decrease the clearance of intravenously administered cyclosporine, it allowed a significant reduction in oral cyclosporine cost without apparent adverse effects on graft function. Further work is needed to determine the effect of CCBs on cyclosporine pharmacokinetics, especially with respect to their metabolism by gut and hepatic cytochrome P-450 enzymes, and their effect on patient outcome.

Administration, Oral↗
PubMed1993

Early prediction of renal allograft loss beyond one year.

Despite significant improvements in the results of renal transplantation since the introduction of cyclosporin, graft loss beyond the 1st year remains a significant and unresolved problem. In a retrospective analysis, 348 cyclosporin-treated renal transplant recipients with a functioning graft at 12 months were studied. Forty-eight patients in whom graft failure occurred in the 2nd and 3rd years were compared to 300 patients who maintained graft function beyond this time. Both groups were comparable with respect to donor and recipient features. Factors reflecting recipient immunological responsiveness--sensitization, previous transplantation and early rejection episodes--continued to affect graft survival beyond the 1st year. Surprisingly, there was a higher incidence of prior transfusion in the group with graft failure in the 2nd and 3rd years than in those with longer function (65% vs 24%). Serum creatinine levels at 3 and 6 months were also predictive of graft loss amongst patients with a functional graft at 1 year. It remains to be answered whether new immunosuppressive drugs and strategies will overcome these risks for late graft loss.

Adult↗
PubMed1991

Cell counts and maps in the larval central nervous system of the ascidian Ciona intestinalis (L.).

Although the ascidian tadpole larva harbors a prospectively valuable prototype of the chordate nervous system, with extensively characterized neural plate cell lineages, the simple cellular composition of the resultant central nervous system (CNS) is not documented in detail. The average total number of cells in the larval CNS of Ciona intestinalis is 335 (range +/- 4, n = 3), 65 or 66 of which reside in the nerve cord of the tail. The estimates were made by tracing and counting the number of nuclei in serial semithin (1 micron) sections cut longitudinally through three larvae, fixed no later than 2 hours after hatching. Within a single fourth larva, L4, 266 cells constituted the CNS in the trunk region of the larva, 45 of which occurred within the visceral ganglion, 215 in the sensory vesicle, and 6 in the neck between the two. Each cell was assigned to one of thirteen categories. Most (182, roughly 68%) are classified as ependymal, a specialized non-neural cell peculiar to embryonic and larval chordates, from their position lining the cavities of the neural tube's elaborations or from clear similarities in the cytological appearance to those that do. Five cells are accessory cells of the sensory structures: three lens cells and a pigment-cup cell in the ocellus, and a single pigment cell in the otolith. Of the remaining 79 cells, 36 are sensory, 17 receptors in the ocellus and 19 presumed hydrostatic pressure receptors; these lie on the right and left sides of the sensory vesicle, respectively. Eighteen of the visceral ganglion cells have been tentatively classified as neurons, as have the remaining 25 cells which form two clusters in the posterior region of the sensory vesicle.

Animals↗
PubMed1988

Development of the central nervous system of the larva of the ascidian, Ciona intestinalis L. I. The early lineages of the neural plate.

The early lineages of the larval central nervous system (CNS) of the ascidian, Ciona intestinalis, have been traced using scanning electron microscopy (SEM) of embryos fixed at 12-min intervals. The CNS precursors lie superficially, exposed for a long portion (9.3 hr of 42%) of embryonic development, in the neural plate. In the 64-cell stage embryo the neural plate contains 10 cells; in all but the first vegetal division these divide with transverse cleavage planes. Synchrony is progressively lessened, but temporal sequence is always exact. Successive divisions occur initially at 30-min intervals. Our analysis confirms existing lineage descriptions for the neural plate up to the end of gastrulation and advances the lineage record through the crucial and temporally complex ninth cleavage, during which cells divide by the following rules: medial cells in each row divide first; the anterior row of vegetal daughter cells divides before their posterior siblings; the posterior row of animal daughter cells divide before their anterior siblings. All cells attain their 10th generation, but four cannot be followed by SEM. In preparation for neurulation the neural plate then comprises 76 cells, forming up to four rows each of eight vegetal hemisphere cells located on the dorsal surface of the embryo, anterior to the blastopore, and eight rows each of six animal hemisphere cells, located anterior to the rows of eight. The temporal and spatial patterns of early cleavage stages have been confirmed in vivo by observations using Nomarski optics.

Animals↗
PubMed1988

Development of the central nervous system of the larva of the ascidian, Ciona intestinalis L. II. Neural plate morphogenesis and cell lineages during neurulation.

We describe the lineage and morphogenesis of neural plate cells in the ascidian, Ciona intestinalis, from reconstructed cell maps of embryos at 12-min intervals during and after neurulation, between 31 and 61% of embryonic development. Neurulation commences in a posterior to anterior wave following in the wake of the ninth cleavage, when all cells, except possibly four, are in their 10th generation. The neural plate then comprises 76 cells, in up to four posterior rows each of eight vegetal-hemisphere cells, and eight anterior rows each of six animal-hemisphere cells. Two cells are lost from the neural plate to the muscle cell line during neurulation and four cells are gained from ectoderm outside the plate. All cells become wedge-shaped. Simple, stereotyped positional changes transform cells from lateral locations in the plate to posterior locations in the tube; bilateral partners shear their midline positions to form the keel, and ectodermal cells zipper up dorsally to form the capstone, of a tube which is four cells in cross section posteriorly, but more complex anteriorly. Neither cell death nor migration occur during neurulation. Divisions become asynchronous and the cell-cycle extends; 170 10th- to 12th-generation cells exist by the time the neural tube becomes completely internalized. Generally, only one further division is required to complete the lineage analysis, two at the most. Neural plate cell divisions were invariant using our observational methods, and their lineage is compared with that from recent studies of H. Nishida (1987, Dev. Biol. 121, 526-541).

Age Factors↗
PubMed1987

The role of genes LAC1 and LAC2 in the biosynthesis of lactose metabolism enzymes by Kluyveromyces lactis.

By crossing different Kluyveromyces lactis strains, the role of genes LAC1, LAC2 and of gene C were analyzed. These genes are involved in the biosynthesis of enzymes for the metabolism of lactose and galactose. They control the biosynthesis of the lactose and galactose transport, of beta-galactosidase and of the three enzymes of the Leloir pathway. The presence of at least one of the LAC gene is required for the biosynthesis to occur. The gene C seems to code for a negative factor which blocks the expression of the LAC1 and LAC2 genes in the absence of an inducer.

Biological Transport↗
PubMed1982

An analysis of the number and composition of the synaptic populations formed by photoreceptors of the fly.

The photoreceptors terminals of newly enclosed female flies, Musca domestica, have been sampled in the first optic neuropile (or lamina) in one of two ways: first, in large number (n = 760) from single sections and second, from serial electron micrographs of the six terminals within each of three cartridges. Both sampling methods concur in assessing the number of synapses established with the two principal monopolar relay interneurons, L1 and L2, within each cartridge. Each receptor is calculated to be presynaptic at about 200 +/- 40 (2 SE) synapses. This value considerably exceeds previous estimates, primarily because we took careful account of the appearance of synapses in different section planes. The number of these synapses correlates highly with the area of receptor terminal presynaptic membrane, so that each synapse is allotted, on average, about 1.6 micrometer2. The synapses are evenly graded in their distribution with an unexplained 23% decrease in both membrane perimeter and synapse number halfway along their receptor terminal's length. The numbers of synapses per receptor did not vary systematically within two horizontal (3 X 20 cartridge) strips of frontal, equatorial lamina sampled. Individual synapses are elongate tetrads (Burkhardt and Braitenberg, '76) with two pairs of postsynaptic elements. The first pair is invariably contributed by the interneurons L1 and L2 (one each). The second pair comes either from the alpha processes of an amacrine cell or from a glial cell. In the distal lamina, however, L3 contributes one of the two postsynaptic processes, the second being alpha or glial. The overall ratio of postsynaptic involvement at distal synapses (alpha: glial: L3) is 55%, 20%, and 12% respectively, the remainder being unidentified.

Animals↗
PubMed1982

Regulation in the number of fly photoreceptor synapses: the effects of alterations in the number of presynaptic cells.

At the equator of the fly's eye, between dorsal and ventral eye halves, a systematic, natural addition of photoreceptor terminal input occurs at each of the fixed populations of uniquely identifiable postsynaptic interneurons in each cartridge of the first optic neuropile, or lamina. The equatorial cartridges are identical in composition except in having seven and eight receptor terminals (7R and 8R, respectively), compared with six elsewhere (6R cartridges). The effects of this augmented presynaptic input upon the frequency of the chief afferent class of photoreceptor tetrad synapse were studied compared with control data for 6R cartridges (Nicol and Meinertzhagen, '82). The synapse population size and distribution within five depth levels of the lamina is, on average, approximately constant for all receptor terminals whether from 6R, 7R, or 8R cartridges. The overall determinant of synapse frequency is therefore presynaptic. Small (5-6%) average decreases in synapse frequency per receptor in 7R and 8R cartridges compared with 6R co-vary with similar decreases in membrane area, each synapse occupying a patch of membrane of similar area in all cases. The tetradic postsynaptic composition of synapses was also similar in all cases. Because of the augmented synaptic input to the postsynaptic neurons, a morphometric analysis was undertaken of two (L1 and L2), which receive input as a pair from every synapse. There is the same dendrite number (about 180) in 8R L1/L2 as in 6R L1/L2 but they have different branching patterns, conforming to the different number and configuration of receptor terminals. Thus in an 8R cartridge each terminal is serviced by a comb of fewer dendrites, but each dendrite is longer, fatter, and services more synapses. The area of L1/L2 dendritic membrane exposed is increased, compared with 6R cartridges, in proportion with the number of synapses it participates at postsynaptically, so that all dendrites (6R and 8R) allocate the same mean area (about 0.55 micrometer2) of postsynaptic membrane per synapse.

Animals↗