Search PubMed⌕ Search

Biomedical subjects

R Nicholson

Publications and source records attributed to R Nicholson.

At least 19 recordsLinked to original sources

Noradrenergic receptor mRNA expression in adult rat superficial dorsal horn and dorsal root ganglion neurons.

Noradrenaline (NAdr) has well documented analgesic actions at the level of the spinal cord. Released from bulbospinal projections onto superficial dorsal horn (SDH) neurons, NAdr modulates the excitability of these neurons through the activation of alpha1, alpha2 or beta adrenoceptors. This study utilised in situ hybridisation to determine the specific expression of adrenoceptors within adult rat lumbar SDH and dorsal root ganglion (DRG) neurons, and reports the presence of alpha1A, alpha1B, alpha2B, beta1 and beta2 adrenoceptor mRNA within SDH neurons, and the presence of alpha1A, alpha1B and alpha2C adrenoceptor mRNA within DRG neurons. The present study provides an insight into the modulation of sensory processing at the level of the spinal cord following adrenoceptor activation.

Animals↗

Serotonin receptor mRNA expression in rat dorsal root ganglion neurons.

In the present study, we have used in situ hybridization to examine the distribution of serotonin (5-HT) receptors in rat dorsal root ganglion (DRG) neurons. Within DRG neurons, mRNAs for 5-HT1B, 5-HT1D, 5-HT2A, 5-HT2B, 5-HT3B and 5-HT4 receptors were readily detected in small (<25 microm), medium (25-45 microm) and large (>45 microm) diameter neurons. In contrast mRNAs for 5-HT1A, 5-HT1E, 5-HT2C, 5-HT5A, 5-HT5B, 5-HT6 and 5-HT7 receptors were undetectable in these neurons. The present study provides an insight into the molecular profile of 5-HT receptor subtypes in neurons responsible for modulating sensory information.

Animals↗

Primary radiation outside the imaged volume of a multislice helical CT scan.

Multislice helical CT scanning has advantages of speed and X-ray tube loading, making it possible to image larger volumes in a single exposure. Our aim is to investigate dose implications for short scans from the additional X-ray tube rotations required to reconstruct a given volume in helical scanning. To this end a multislice scanner was compared with a single slice scanner. Two independent methods were used. The first was based on optical density measurements taken from a film exposed free-in-air as it moves with the CT bed along the scan axis. The second used measurements from a pencil ionization chamber supported free-in-air at the centre of the CT aperture for the duration of both a long scan and a short scan. This method assumes the same excess primary radiation at the extremes of both scans and the measurements are incorporated into two simultaneous equations. The dose-length product outside the imaged volume has been compared with the dose-length product inside the imaged volume using both methods. For 4 x 5 mm multislice collimation with a 360 degrees interpolation and a pitch of 0.875, the film and simultaneous equations methods show an excess dose-length product at the extremes of the scan volume equivalent to 3.3 cm and 3.5 cm extra scan length, respectively. This represents a large percentage of a short scan and is substantially greater than for a helical scan using the single slice scanner with 5 mm collimation, a 360 degrees interpolation and a pitch of 1. The latter showed an excess dose-length product at the extremes which was equivalent to 0.35 cm scan length by the film method and 0.25 cm using simultaneous equations. Taking the abdominal protocols recommended by the respective manufacturers, however, the multislice scanner could cover a 45 cm scan length in a single exposure, while the single slice scanner needed six exposures to image the same volume. With the multislice scanner set at 4 x 2.5 mm collimation, 360 degrees interpolation and a pitch of 0.875, the dose-length product outside the volume of interest was equivalent to 1.9 cm scan length by the first method and 1.8 cm using the second method. With 4 x 1 mm collimation it was equivalent to 1.0 cm using both methods. Changing the interpolation algorithm from 360 degrees to 180 degrees had no effect on the additional equivalent scan length while doubling the pitch resulted in a 25% increase. We conclude from this study that with the multislice scanner, the axial mode is to be preferred for short CT scans such as those used in patient biopsies and drainage. For paediatric helical scans shorter than 13 cm, dose length product is reduced by using 4 x 2.5 mm rather than 4 x 5 mm collimation. For longer scans, however, the increased CT dose index associated with narrower collimation in the multislice mode offsets the dose reduction at the extremes.

Humans↗

Development and reproducibility of a brief food frequency questionnaire for assessing the fat, fiber, and fruit and vegetable intakes of rural adolescents.

OBJECTIVE: To describe the systematic development and reproducibility of a food frequency questionnaire (FFQ) designed to meet the specific research requirements of the Goals for Health cancer prevention intervention program for rural middle school children. DESIGN: A 4-step process was used to develop a brief FFQ for scoring intakes of total fat, fiber, and fruits and vegetables. The resulting questionnaire consisted of 25 food frequency items and 10 supplemental questions. Reproducibility of the questionnaire was determined by comparing responses at the beginning and end of a 4-month interval. SUBJECTS: Study subjects were sixth- and seventh-grade students attending middle schools in rural areas of Virginia and upstate New York. Seventh-grade students participated in the pilot study, and sixth-grade students participated in the reproducibility study. The final version of the FFQ was completed twice by 539 sixth graders. After exclusions for missing and unreliable data, the usable sample size was 415. Boys were somewhat more likely than girls to be excluded for missing data. African-American students comprised 32% of the population. STATISTICAL ANALYSES PERFORMED: Each food frequency item was associated with 3 scores--a fat score, a fiber score, and a combined score for the number of servings of fruits and vegetables. Means and standard deviations were determined for nutrient variables, differences between repeat administrations were tested for significance by paired t test, and Pearson correlation coefficients were calculated for nutrients and for individual food items. RESULTS: Correlation coefficients for nutrient scores were 0.58 for fat, 0.49 for fiber, and 0.51 for fruits and vegetables. For individual food items, correlations ranged from 0.24 to 0.59 (mean=0.41). APPLICATIONS/CONCLUSIONS: Using a systematic approach to developing a study-specific FFQ for rural adolescents is feasible. Further, the reproducibility of the Goals for Health questionnaire was demonstrated for the 3 nutrient scores it was designed to measure. This developmental approach may be readily adapted to other populations, study designs, and nutrients of interest. The validity of the questionnaire remains to be tested.

Adolescent↗

Change in expression of ER, bcl-2 and MIB1 on primary tamoxifen and relation to response in ER positive breast cancer.

Pre-treatment oestrogen receptor (ER) expression in breast cancer predicts for rate of response to endocrine therapy but not for the quality or duration of response (DofR). ER is known to be down-regulated by anti-oestrogens. This study has tested the hypothesis that the degree of down-regulation of ER and the ER-regulated marker bcl-2 are associated with the quality and duration of tamoxifen response. 80 patients with ER+ve breast cancer (H-score > 10) receiving primary tamoxifen (n = 51 Stage I-II elderly; n = 29 Stage III) underwent sequential tumour biopsies for immunocytochemical assessment of ER, bcl-2 and the proliferation marker MIB1. Median follow-up is 45 months. By 6-months on therapy three patients had attained complete response (CR), 27 partial response (PR); 44 static disease (SD) and six progression (PD) by UICC criteria. Greater decrease in ER and bcl-2 H-score from pre-treatment to 6 weeks (p = 0.035, p = 0.037) and ER and bcl-2 H-score from pre-treatment to 6 months (p = 0.058, p = 0.036) were significantly associated with better quality of response (CR/PR vs SD/PD). Greater 6-week and 6-month reduction in bcl-2 H-score (p = 0.041, p = 0.036) and 6-week reduction in MIB1 (p = 0.013) were significantly correlated with longer DofR. This study demonstrates that greater down-regulation of ER and the ER-regulated protein bcl-2 on primary tamoxifen are significantly associated with a better quality of response and bcl-2 and the proliferation marker MIB1 a longer duration of response in ER+ve breast cancer.

Aged↗

Another look at LREC annual reports.

Almost the only readily available sources of information about the activities of UK research ethics committees are the annual reports that they have been required since 1991 to publish. This paper reports on a further study of those reports by the Bulletin.

Committee Membership↗

PMP22 carrying the trembler or trembler-J mutation is intracellularly retained in myelinating Schwann cells.

Missense mutations in the murine peripheral myelin protein-22 gene (Pmp22) underly the neuropathies in the trembler (Tr) and trembler-J (Tr-J) mice and in some humans with Charcot-Marie-Tooth disease. We have generated replication-defective adenoviruses containing epitope-tagged, wild-type-, Tr-, or Tr-J-PMP22 bicistronic with the Lac-Z reporter gene. These viruses were microinjected into the sciatic nerves of 10-day-old Sprague-Dawley rats and, later, analyzed by immunohistochemistry to determine the distribution of mutant protein in infected myelinating Schwann cells. We found that epitope-tagged, wild-type PMP22 is successfully transported to compact myelin, whereas the Tr and the Tr-J mutant proteins are retained in cytoplasmic compartment, colocalizing with the endoplasmic reticulum. These results provide in vivo evidence that the pathogenesis of the Tr and Tr-J mutations are most likely a function of abnormal retention within the endoplasmic reticulum of myelinating Schwann cells.

Adenoviridae↗

Sustained mammary gland-directed, ponasterone A-inducible expression in transgenic mice.

The ability to regulate temporal- and spatial-specific expression of target genes in transgenic mice will facilitate analysis of gene function and enable the generation of murine models of human diseases. The genetic analysis of mammary gland tumorigenesis requires the development of mammary gland-specific transgenics, which are tightly regulated throughout the adult mammary epithelium. Analysis of genes implicated in mammary gland tumorigenesis has been hampered by mosaic transgene expression and the findings that homozygous deletion of several candidate genes (cyclin D1, Stat5A, prolactin receptor) abrogates normal mammary gland development. We describe the development of transgenic mouse lines in which sustained transgene expression was inducibly regulated, both specifically and homogeneously, in the adult mammary gland epithelium. Transgenes encoding RXRalpha and a chimeric ecdysone receptor under control of a modified MMTV-LTR, which targets mammary gland expression, were used. These transgenic 'receptor' lines were crossed with transgenic 'enhancer' lines in which the ecdysone/RXR binding site induced ligand-dependent expression of transgenic beta-galactosidase. Pharmacokinetic analysis of a highly bioactive ligand (ponasterone A), identified through screening ecdysteroids from local plants, demonstrated sustained release and transgene expression in vivo. This transgenic model with both tightly regulated and homogeneous transgene expression, which was sustained in vivo using ligands readily extracted from local flora, has broad practical applicability for genetic analysis of mammary gland disease.

Animals↗

The cross-leg soleus muscle flap.

Reconstruction of the lower limb can be a difficult problem, especially when located over the lower third of the leg, or when a large soft-tissue defect exists. When local flap coverage is not possible, a distant flap--free or pedicled--is indicated. There are, however, circumstances that preclude the use of a free flap, and in these situations cross-leg flaps remain a viable alternative. They have been proved to be safe, are usually quick to perform, and do not require specialized facilities for postoperative monitoring. A new variation of the soleus muscle flap--the cross-leg soleus muscle flap--is described. Using this modification, the authors successfully closed large defects of the lower limb in 9 patients. The donor site defect that is left on the contralateral limb is far more acceptable than that left by conventional cross-leg fasciocutaneous or musculocutaneous flaps. The authors prefer the cross-leg soleus flap to conventional cross-leg flaps in these situations.

Adult↗

Skin sparing in interventional radiology: the effect of copper filtration.

Complex and lengthy interventional radiological techniques have resulted in a number of patients developing skin reactions in recent years. To safeguard against these side effects, we have investigated the degree to which entrance skin dose can be reduced by inserting 0.18 mm and 0.35 mm copper filtration in the incident beam. The potential reduction was measured on a 22 cm water phantom for each of eight models of a fluoroscopy unit. Using the catheter laboratory fluoroscopy unit on which radiofrequency ablations are routinely performed, we assessed the relative effectiveness of adding filtration and increasing the kV:mA ratio. Image quality was subjectively assessed for diagnostic and therapeutic acceptability in two groups of 10 patients undergoing radiofrequency ablations, pacemaker insertions or electrophysiology studies. One of the groups was screened with 0.35 mm copper filtration in place and the other group acted as the control. Maximum patient skin dose proved difficult to measure directly because of the unpredictable dose pattern. This pattern was studied in four patients using a film method in conjunction with thermoluminescent dosemeters. Copper filtration 0.35 mm thick inserted in the beams of the eight fluoroscopy units produced a mean reduction in entrance dose to the phantom of 58% with a mean increase in tube loading of 29%. At 100 kV the increased loading on the X-ray tube was equivalent to increasing the anteroposterior separation of the patient by 2 cm. Measurements on the catheter laboratory unit showed that the tube voltage would need to be raised above the normal diagnostic range to obtain an equivalent entrance dose reduction without the filter. The blackening of films under the patients showed complex patterns, but the estimated skin doses were consistent with those predicted by the phantom experiments. All six cardiologists considered there to be insignificant detriment to image quality in the procedures investigated.

Copper↗

Effect of a full and empty bladder on radiation dose to the uterus, ovaries and bladder from lumbar spine CT and X-ray examinations.

This is a quantitative study of the effect of a full and empty bladder on the position of the uterus, ovaries and bladder relative to the lumbar spine. Data are used to estimate the difference in radiation dose to these organs from performing a lumbar spine CT investigation or a lateral lumbar spine radiograph with a full bladder compared with an empty bladder. 12 women of child-bearing age underwent pelvic magnetic resonance scans with full and empty bladders. The positions of the uterus, ovaries and bladder were matched with the radiation dose distribution that would have occurred either side of the inferior boundary of the CT scan volume and the lateral lumbar spine radiograph. These radiation dose profiles were measured on phantoms using a combination of ionization chambers and thermoluminescent dosemeters. When the bladder was emptied, the mean position of the endometrial cavity fundal tip moved from 4.1 cm to 6.1 cm inferior to the centre of the L5/S1 disc space, and from 0.87 cm to 1.12 cm anterior to the centre of the L5/S1 disc space. This movement on micturation would have reduced the mean dose to the uterine internal fundal tip during a pelvic CT scan from 6.8 mGy to 3.9 mGy, which represents a mean reduction of 43% (range 12-67%). The mean dose from a lateral lumbar spine examination would have been reduced from 197 microGy to 126 microGy. The change in ovary position results in the mean ovary dose being reduced by 48% for the lumbar spine CT scan and by 43%) for a lateral lumbar spine radiograph. When the bladder was emptied, the average position of the bladder wall moved from 7.2 cm to 10.3 cm inferior to the L5/S1 disc space. This change in bladder position reduces the mean dose to the wall of a full bladder from 5.7 mGy for a CT scan and 114 microGy for a lumbar spine radiograph to 2.2 mGy and 42 microGy, respectively, for an empty bladder.

Adult↗

Efficacy of chest CT in a pediatric ICU: a prospective study.

STUDY OBJECTIVES: (1) To determine whether chest CT provides additional information compared with chest radiography regarding the nature of intrathoracic disease in critically ill children, (2) to determine whether such information alters clinical management, (3) to assess the role of a low-dose high-resolution CT (HRCT) protocol in pediatric ICU (PICU) patients. DESIGN: Prospective study. SETTING: Specialized PICU in a teaching hospital serving London and the south of England. PATIENTS: Twenty children (age range, 3 weeks to 12 years; median, 11 months) underwent chest CT during a 33-month period. Inclusion criteria were (1) inconclusive diagnosis from chest radiograph (CXR) or (2) CXR appearances inconsistent with high oxygenation or ventilatory requirements (PaO(2) to fraction of inspired oxygen ratio < 30 or mean airway pressure > 15 cm H(2)O). INTERVENTIONS: Low-dose HRCT scans (50 mA, 2-mm slice thickness at intervals of 10 or 15 mm) were performed on 12 patients, and helical CT (50 to 250 mA; pitch, 1 to 1.5) performed on 8 patients. MEASUREMENTS AND RESULTS: CT provided additional information regarding the nature of intrathoracic disease in 17 of 20 patients (85%) and resulted in changes to subsequent clinical management in 12 of 20 patients (60%). CONCLUSIONS: Chest CT can add to the accuracy of intrathoracic diagnosis provided by the CXR and may directly influence the acute management of critically ill children. The CT protocol should be tailored to the clinical and radiologic question posed for each individual patient. Noncontiguous HRCT can often provide accurate assessment of pulmonary parenchymal and pleural disease at a reduced radiation dose compared with helical CT.

Child↗

Microchimerism and blocking activity in women with recurrent spontaneous abortion (RSA) after alloimmunization with the partner's lymphocytes.

Alloimmunization therapy using the partner's leukocytes has been reported to be effective in preventing the failure of pregnancy in patients who have suffered RSA of unknown cause. After alloimmunization, several investigators have reported the presence of blocking factors (BF) in women with successful pregnancies in in vitro assays of lymphocyte response. The recent discovery of small numbers of ubiquitous donor cells (microchimerism) in human transplants up to 29 years post-transplantation has raised questions about the migration of the chimeric cells and their role in the induction and perpetuation of tolerance. We have investigated the production of BF in the mixed lymphocyte reaction (MLR) before and in some patients after alloimmunization and its possible relation with the development of microchimerism (M). Before the treatment we studied 14 couples with three or more abortions who were evaluated clinically to rule-out genetic, structural, endocrine, infectious and autoimmune causes. The M study was done by nested PCR-SSP technique with HLA-DR alleles, before and after 30 days of the last immunization. Before the treatment only one patient was M positive and none were BF positive with inhibition effect (IE) > 50. Only eight underwent treatment. The patients had between three and nine alloimmunizations (x = 4.7). After treatment, all patients were M positive with IE > 50. Six months after the last immunization, four patients are M positive with IE > 50. In conclusion, the hypothesis proposes that alloimmunization establishes a state of microchimerism that would be the necessary allogeneic stimulus for T-cell activation, and the induction or maintenance of tolerance to the fetus during pregnancy. reserved.

Abortion, Habitual↗

Trends in hospitalization and mortality from rotavirus disease in New Zealand infants.

BACKGROUND: Rotavirus illness is associated with significant morbidity and mortality worldwide. We have examined trends in diarrheal disease in New Zealand children to determine the disease burden attributable to rotavirus and to estimate the proportion of hospitalizations preventable by vaccination. METHODS: Hospital admissions data and laboratory records for 1994 to 1996, were obtained for children 0 to 4 years at four sites (serving -60% of the New Zealand population). Rotavirus disease burden was estimated using combined admissions and laboratory data. Severity of disease was estimated in a sample of 150 hospitalizations for rotavirus diarrhea, and the proportion of vaccine-preventable admissions was extrapolated. Mortality attributed to diarrheal causes was determined from national records for 1974 to 1993. RESULTS: Between 1994 and 1996, 4436 children <5 years of age were hospitalized with diarrhea (1047/100000 children per year). Admissions associated with rotavirus were estimated at 1522 to 1535 (315 to 362/100000 annually). Infants between 6 and 17 months were most commonly affected (42% of all cases). More male children than female children were hospitalized (P < 0.001) and mean length of stay was calculated as 1.51 days (SD 2.35). Disease severity scoring revealed that 61.3 and 38.0% of admissions reviewed were severe and very severe, respectively. Deaths from diarrheal causes numbered 138 among children 0 to 4 years old for the 20-year period 1974 to 1993, with 18 deaths occurring between 1984 and 1993 (10 years). CONCLUSION: Current vaccines control severe disease, suggesting that 72% of cases reviewed would be eligible for prevention. A full cost effectiveness analysis is required to demonstrate anticipated benefits of vaccination.

Child, Preschool↗

One size fits all: a surgical technique for the correction of all types of prominent ears.

Patient satisfaction after surgery to correct the prominent ear relates to the degree of retroposition of the ear. Angular breaks in the cartilage seen with other cartilage-transecting procedures (and even after conchal resections), which are noticed by patients, led to the development of this technique. It is an easy operative technique that may be modified to suit all prominent ears, including the constricted cup ear, and it does not leave any sharp, visible ridges in the region of the anti-helix or concha. The procedure combines and modifies a number of techniques that have been described previously, which allows more flexibility in the treatment of this deformity.

Decision Trees↗