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Biomedical subjects

A Charles

Publications and source records attributed to A Charles.

At least 19 recordsLinked to original sources
PubMed2003

Effect of fatigue on performance measured by a driving simulator in automobile drivers.

OBJECTIVE: To identify risk factors of performance decrement in automobile drivers. METHODS: 114 drivers (age <30 years, n=57; age > or =30 years, n=57) who stopped at a rest stop area on a freeway were recruited for the study. They filled out a questionnaire on their journey, sleep/wake patterns and performed a 30-min test on a driving simulator. The test evaluates, by computerized analysis, the lateral deviation of a virtual car from an appropriate trajectory on a virtual road. A sex/age matched control group was recruited in the community. Control subjects were studied at the same time of day as the index case driver. Controls had normal sleep wake schedule, absence of long driving and performed the same driving test. RESULTS: Drivers performed significantly worse than controls on the driving test. Age and duration of driving were the main factors associated with decreased performance. CONCLUSION: Our driving simulator can identify fatigue generated by driving but results must be considered in relation with age of subjects.

Adolescent↗
PubMed2001

Regulation of gonadotropin-releasing hormone release by cyclic AMP signalling pathways.

The frequency and amplitude of gonadotropin-releasing hormone (GnRH) pulses are tightly regulated for the maintenance of reproductive cycles. Pulsatile GnRH release was shown to be an intrinsic property of murine GT1 GnRH neurons, and primate placodal GnRH neurons. GT1 neurons show spontaneous action potentials that are associated with Ca2+ oscillations and hormone secretion. Increased cyclic AMP (cAMP) levels in GT1 neurons appear to stimulate GnRH release by activation of cAMP-gated cation (CNG) channels. Activation of the CNG channels correlated with increased neuron excitability and Ca2+ oscillations. Activation of protein kinase A is not necessary for cAMP-induced stimulation of GnRH secretion, but appears to activate negative feedback pathways. Potential negative feedback pathways may decrease cAMP levels by inhibiting adenylyl cyclase V, and activating the phosphodiesterase, PDE4D3. These stimulatory and inhibitory cAMP-signalling pathways appear to regulate the excitability of the GT1 neurons, and may constitute a biological clock timing the pulsatile release of GnRH.

Adenylyl Cyclases↗
PubMed2001

The role of comparative genomic hybridisation in prenatal diagnosis.

The aims of this study were to assess the feasibility of using comparative genomic hybridisation instead of conventional cytogenetics in prenatal diagnosis and to determine the size of DNA loss that can be detected. Using comparative genomic hybridisation, six cases with standard aneuploidies were diagnosed correctly. This technique clearly identified a partial duplication of the long arm of chromosome 1 but was not capable of detecting the associated inversion. A small interstitial deletion on short arm of chromosome 10 also was detected precisely. Although the current comparative genomic hybridisation resolution is similar to the sensitivity of the highest resolution G banding, the latter is not a routine strategy in prenatal diagnosis. Comparative genomic hybridisation can allow full chromosome assessment equal to the highest resolution cytogenetic studies without the need for cell culture.

Cytogenetic Analysis↗
PubMed2001

Inhibition of bacterial superantigens by peptides and antibodies.

The pyrogenic exotoxins of group A streptococci and staphylococcal enterotoxins are a family of structurally related superantigens with similar biological activity. Two distinct areas have been identified which have a highly conserved amino acid homology in all of the toxin families. A number of peptides were constructed from these regions, some of which were concatenated and polymerized to enhance their immunogenicity in animals. Antibodies prepared against these polymerized peptides were used to serologically identify the majority of the superantigen toxins, block the biological activities of the superantigens, and protect an experimental animal model against shock. In addition certain peptides were able per se to block up to 90% of the proliferative responses induced by the toxins. The peptide also proved protective in a septic shock model in mice. Binding experiments indicate that the peptide binds tightly to the major histocompatibility complex class II molecule, thus preventing binding and hence activation of the superantigen. The selective and rapid binding of the peptide to the major histocompatibility complex class II molecule may lead to a novel therapeutic modality in treatment of superantigen-mediated diseases.

Amino Acid Sequence↗
PubMed2001

cAMP modulates the excitability of immortalized H=hypothalamic (GT1) neurons via a cyclic nucleotide gated channel.

GT1 cells are immortalized hypothalamic neurons that show spontaneous bursts of action potentials and oscillations in intracellular calcium concentration [Ca(2+)](i), as well as pulsatile release of GNRH: We investigated the role of cyclic nucleotide gated (CNG) channels in the activity of GT1 neurons using patch clamp and calcium imaging techniques. Excised patches from GT1 cells revealed single channels and macroscopic currents that were activated by either cAMP or cGMP. CNG channels from GT1 cells showed rapid transitions from open to closed states typical of heteromeric CNG channels, were selective for cations, and had an estimated single channel conductance of 60 picosiemens (pS). Ca(2+) inhibited the conductance of macroscopic currents and caused rectification of currents at increasingly positive and negative potentials. The membrane permeant cAMP analog Sp-cAMP-monophosphorothioate (Sp-cAMPS) increased the frequency of spontaneous Ca(2+) oscillations in GT1 cells, whereas the Rp-cAMPS isomer had only a slight stimulatory effect on Ca(2+) signaling. Forskolin, norepinephrine, and dopamine, all of which stimulate cAMP production in GT1 cells, each increased the frequency of Ca(2+) oscillations. The effects of Sp-cAMPS or NE on Ca(2+) signaling did not appear to be mediated by protein kinase A, since treatment with either H9 or Rp-cAMPS did not inhibit the response. The CNG channel inhibitor L-cis-diltiazem inhibited cAMP-activated channels in GT1 cells. Both L-cis-diltiazem and elevated extracellular Ca(2+) reversibly inhibited the stimulatory effects of cAMP-generating ligands or Sp-cAMP on Ca(2+) oscillations. These results indicate that CNG channels play a primary role in mediating the effects of cAMP on excitability in GT1 cells, and thereby may be important in the modulation of GnRH release.

Adrenergic alpha-Agonists↗
PubMed2000

Identification of differential methylation of the WT1 antisense regulatory region and relaxation of imprinting in Wilms' tumor.

Wilms' tumor (WT) is associated with loss of heterozygosity at chromosome 11p13, the site of the Wilms' tumor suppressor gene, WT1. Although the preferential loss of maternal alleles suggested that differential allelic expression of WT1 might occur, this has not been evident in normal fetal tissues or WTs. In this study, we show that the WT1 antisense regulatory region is differentially methylated, with Southern blot analysis of four loss of heterozygosity-negative WTs and their corresponding normal kidneys indicating that allelic methylation is lost in WTs. Reverse transcription-PCR expression analysis correlates methylation with monoallelic expression of the antisense WT1 transcript (WT1-AS) in normal kidney. However, WTs display hypomethylation and biallelic expression of WT1-AS. Our findings are consistent with imprinting of WT1-AS in normal kidney and the relaxation of imprinting in Wilms' tumorigenesis. This identifies the WT1 antisense regulatory region in intron 1 as a primary site for epigenetic deregulation at chromosome 11p13 in WTs.

Alleles↗
PubMed1999

Suturing of minor lacerations by clinical nurse specialists in the emergency department.

A programme enabling clinical nurse specialists (CNS) to suture minor lacerations in the emergency department (ED) was implemented at Monash Medical Centre (MMC), Melbourne, Australia. A descriptive comparative design was used to evaluate the programme. Patients meeting the inclusion criteria of the project were randomly assigned to group 1 (the medical group) and group 2 (the CNS group). Analysis of the data found that patient length of stay was not significantly different between the two groups. However, those patients cared for by the CNS group appeared to be more satisfied with their care and the overall services received. Wound healing outcomes were found to be similar between the CNS sutured group and those sutured by medical staff. The implementation of this new role for CNS in the ED appeared to be successful from the point of view of patient outcomes.

Adolescent↗
PubMed1999

Paediatric community vision screening--a new model.

The purpose of this study was to establish if a community based model using a Hospital Optometrist and Community Orthoptist can provide a practical secondary vision screening service for children. These professionals working in an Inner London Health Centre, assessed children who had failed primary vision screening. In total 483 new patients were seen between April 1994 and March 1996 with the largest referral source being the school nurse screening programme. The majority were managed by the team with a total onward referral rate to the Hospital Eye Service of 14%. In 78% of these cases the consultant's diagnosis agreed with the reason for referral. Where the consultant's diagnosis differed the children were identified as normal or a variant of normal. This model of care provides a 'one stop service' where a child identified as having a potential visual problem at primary screening can be assessed, refracted and provided with spectacles in a local setting without hospital referral. Referrals to the Hospital Eye Service are considerably reduced and a convenient service is provided for parents and children.

Age Distribution↗
PubMed1998

Central nervous system metastasis in Wilms' tumor: a review of three consecutive United Kingdom trials.

BACKGROUND: Central nervous system (CNS) metastasis is an uncommon event in pediatric oncology, and typically occurs at the end stage of the disease. Previous reports suggest that brain metastases in patients with Wilms' tumor might behave differently. METHODS: This study reviews the data from three consecutive United Kingdom Children's Cancer Study Group trials (UKW 1, 2, and 3) focusing on this entity. RESULTS: Seven children of 1249 (0.6%) entered into Wilms' tumor studies developed CNS metastases between 2-27 months after initial diagnosis. At last follow-up 3 patients still were alive and 4 had died; the mean follow-up from recurrence in the surviving patients was 63 months. Radiotherapy and chemotherapy were administered to all surviving patients. Those patients who died had tumors with particularly aggressive features or extensive disease. CONCLUSIONS: CNS metastasis of Wilms' tumor is not in itself a terminal event. With regard to other sites of recurrence, salvage therapy can be expected to be effective in patients without other adverse prognostic features.

Central Nervous System Neoplasms↗
PubMed1998

Intercellular calcium waves in glia.

Glial cells are capable of communicating increases in [Ca2+]i from a single cell to many surrounding cells. These intercellular Ca2+ waves have been observed in glia in multiple different preparations, including dissociated brain cell cultures, glial cell lines, organotypic brain slice cultures, and intact retinal preparations. They may occur spontaneously, or in response to a variety of stimuli. Ca2+ waves occurring under different conditions in different preparations may have distinctive patterns of initiation and propagation, and distinctive pharmacological characteristics consistent with the involvement of different intracellular and intercellular signaling pathways. This paper presents original data supporting a combination of gap junction and extracellular messenger-mediated signaling in mechanically induced glial Ca2+ waves. Additional new observations provide evidence that a rapidly propagated signal may precede the glial Ca2+ wave and may mediate rapid glial-neuronal communication. This original data is discussed in the context of a review of the literature and current concepts regarding the potential mechanisms, physiological and pathological roles of this dynamic pattern of glial intercellular signaling.

Animals↗
PubMed1998

Uterine side effects of tamoxifen: a need for systematic pretreatment screening.

OBJECTIVE: To determine the effect of tamoxifen on the endometrium in postmenopausal women with breast cancer and to try to identify, by pretreatment screening, subjects at higher risk of developing endometrial cancer. METHODS: Between January 1993 and January 1996, 264 postmenopausal women with breast cancer were studied prospectively with pelvic ultrasonography. Outpatient hysteroscopy and endometrial biopsy were done if ultrasound abnormalities were detected. Initial endometrial evaluation was done before treatment with tamoxifen was started, 20 mg daily, and annually thereafter. Attention was focused on endometrial lesions and, especially, endometrial hyperplasia, which was defined according to World Health Organization classification. Endometrial hyperplasia was subdivided into two broad categories: hyperplasia without cytological atypia and hyperplasia with cytological atypia. Adenocarcinoma in situ was defined as a well-differentiated endometrial carcinoma confined to the endometrial mucosa without myometrial invasion. RESULTS: Forty-six women (17.4%) had asymptomatic endometrial lesions diagnosed before starting tamoxifen, and two of these were atypical lesions. Patients with initial lesions and those without initial lesions were followed separately. At 3 years of follow-up, the incidence of atypical lesions was significantly higher in women with lesions initially than in those without (three lesions among nine women versus one lesion among 51 women, P = .009). CONCLUSION: It appears that a group of high-risk subjects can be defined on the basis of endometrial evaluation before tamoxifen therapy; these women should be followed carefully because of the high incidence of severe atypical lesions.

Adenocarcinoma↗
PubMed1998

[Endometrial evaluation prior to tamoxifen: preliminary results of a prospective study].

The objective of this study was to try to identify, by pretreatment screening, a group of patients at higher risk of developing endometrial carcinoma on tamoxifen. Between January 1993 and January 1997, 360 postmenopausal patients with breast cancer were enrolled in this prospective study. Basal screening included gynaecologic examination with a Papanicolaou smear and endovaginal sonography. In the case of an abnormal ultrasound (endometrial thickness greater than 4 mm), an outpatient hysteroscopy with an endometrial biopsy was carried out. These examinations were repeated annually. By means of this preliminary evaluation, two groups of patients were identified: patients without initial lesions (group I) and patients with initial endometrial lesions (group II). These two groups of patients were followed up separately exactly in the same way. Endometrial lesions taken into account were: adenocarcinomas (in situ and invasive), polyps with or without atypia, myomas and adenomyotic lesions with irregular mucosa. After 3 years and after 4 years of follow-up, the percentage of atypical lesions was significantly higher in the group with initial lesions than in the group without initial lesions. This study suggests that a group of high risk patients more sensitive to the carcinogenic effect of tamoxifen can be identified by pretreatment evaluation.

Adenoma↗