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Biomedical subjects

G Little

Publications and source records attributed to G Little.

At least 19 recordsLinked to original sources
PubMed2006

Oxegen 2004: the impact of a major music festival on the workload of a local hospital.

This prospective observational study was undertaken to assess the impact of a major music festival on the workload of a local hospital. Data were collected on all attendances at Naas General Hospital from the nearby Oxegen 2004 music festival. Patient demographics, disposition and diagnoses were recorded. Emergency department activity levels were compared before, during and after the festival. Seventy-two attendees were referred to Naas emergency department over a 3-day period, representing a 45% increase in the hospital's emergency department attendance rate. Thirty-seven of these attendees (51%) required inpatient or tertiary centre services. Thirty-four attendees (47%) were noted as having consumed alcohol and/or used illicit substances. We conclude that despite the provision of on-site medical facilities, major music events are associated with a significant increase in local health care activity and expenditure.

Adolescent↗
PubMed2004

Patient, carer and health service outcomes of nurse-led early discharge after breast cancer surgery: a randomised controlled trial.

Patients with breast cancer who require axillary clearance traditionally remain in hospital until their wound drains are removed. Early discharge has been shown to improve clinical outcomes, but there has been little assessment of the psychosocial and financial impact of early discharge on patients, carers and the health service. This study aimed to evaluate the effectiveness of a nurse-led model of early discharge from hospital. Main outcome measures were quality of life and carer burden. Secondary outcomes included patient satisfaction, arm morbidity, impact on community nurses, health service costs, surgical cancellations and in-patient nursing dependency. A total of 108 patients undergoing axillary clearance with mastectomy or wide local excision for breast cancer were randomised to nurse-led early discharge or conventional stay. Nurse-led early discharge had no adverse effects on quality of life or patient satisfaction, had little effect on carer burden, improved communication between primary and secondary care, reduced cancellations and was safely implemented in a mixed rural/urban setting. In total, 40% of eligible patients agreed to take part. Nonparticipants were significantly older, more likely to live alone and had lower emotional well being before surgery. This study provides further evidence of the benefits of early discharge from hospital following axillary clearance for breast cancer. However, if given the choice, most patients prefer to stay in hospital until their wound drains are removed.

Aged↗
PubMed2000

Topology of double minutes (dmins) and homogeneously staining regions (HSRs) in nuclei of human neuroblastoma cell lines.

Amplification of the MYCN gene is a characteristic feature of many neuroblastomas and is correlated with aggressive tumor growth. Amplicons containing this gene form either double minutes (dmins) or homogeneously staining regions (HSRs). To study the nuclear topology of these tumor-specific and transcriptionally active chromatin structures in comparison to chromosome territories, we performed fluorescence in situ hybridization with a MYCN probe and various chromosome paint probes, confocal laser scanning microscopy, and quantitative three-dimensional image analysis. The dmins formed dot-like structures in interphase nuclei and were typically located at the periphery of complexly folded chromosome territories; dmins noted in the chromosome territory interior were often detected within an invagination of the territory surface. Interphase HSRs typically formed extremely expanded structures, which we have never observed for chromosome territories of normal and tumor cell nuclei. Stretches of HSR-chromatin often extended throughout a large part of the cell nucleus, but appeared well separated from neighboring chromosome territories. We hypothesize that dmins are located within the interchromosomal domain (ICD) space and that stretches of HSR-chromatin align along this space. Such a topology could facilitate access of amplified genes to transcription and splicing complexes that are assumed to localize in the ICD space.

Cell Nucleus↗
PubMed1999

The 3D positioning of ANT2 and ANT3 genes within female X chromosome territories correlates with gene activity.

The three-dimensional positioning of the X-chromosomal adenine nucleotide translocase genes, ANT2 and ANT3, were compared in the active and inactive X chromosome territories (Xa and Xi) of female human amniotic fluid cell nuclei. ANT2 is located in Xq24-q25 and is transcriptionally active on Xa, but inactive on Xi. ANT3 is located in the pseudoautosomal region Xp22.3 and escapes X-inactivation. Three-color fluorescence in situ hybridization, confocal laser scanning microscopy, and three-dimensional image analysis revealed that transcriptionally active ANT2 and ANT3 genes were positioned more peripheral within their chromosome territory than the inactive ANT2 gene. The position of the latter was significantly more interior in the Xi territory. Although the volumes of both X territories were similar, 3D distances between ANT2 and ANT3 were significantly smaller in Xi compared to Xa territories reflecting different territory shapes. Our data show a correlation between 3D positioning and transcriptional activity of these X-specific genes.

Amniotic Fluid↗
PubMed1998

Spatial distributions of early and late replicating chromatin in interphase chromosome territories.

The surface area of chromosome territories has been suggested as a preferred site for genes, specific RNAs, and accumulations of splicing factors. Here, we investigated the localization of sites of replication within individual chromosome territories. In vivo replication labeling with thymidine analogues IdUrd and CldUrd was combined with chromosome painting by fluorescent in situ hybridization on three-dimensionally preserved human fibroblast nuclei. Spatial distributions of replication labels over the chromosome territory, as well as the territory volume and shape, were determined by 3D image analysis. During late S-phase a previously observed shape difference between the active and inactive X-chromosome in female cells was maintained, while the volumes of the two territories did not differ significantly. Domains containing early or mid to late replicating chromatin were distributed throughout territories of chromome 8 and the active X. In the inactive X-chromosome early replicating chromatin was observed preferentially near the territory surface. Most important, we established that the process of replication takes place in foci throughout the entire chromosome territory volume, in early as well as in late S-phase. This demonstrates that activity of macromolecular enzyme complexes takes place throughout chromosome territories and is not confined to the territory surface as suggested previously.

Cells, Cultured↗
PubMed1997

Effects of clodronate-containing liposomes on testicular macrophages and Leydig cells in vitro.

We undertook the present studies to determine if clodronate-containing liposomes have direct effects on Leydig cells. Macrophages and Leydig cells were isolated and maintained separately in culture. Following treatment with clodronate-containing liposomes, macrophages were killed in a dose-response fashion over a range of 5-200 microliters liposomes. By comparison, a 500 microliters dose was required to kill Leydig cells, but this was not dependent upon clodronate since liposomes containing buffer elicited an identical response. The concentration of testosterone in medium from Leydig cells treated with clodronate-containing liposomes was significantly reduced compared with untreated cells. However, we subsequently found that liposomes can adsorb testosterone. Therefore, testosterone production was determined at various times following removal of liposomes from Leydig cells, thereby circumventing this complication. It was found that testosterone production was not altered by liposomes under these conditions. Finally, free clodronate had no effect on testosterone production, even at doses representing the amount present within the 500 microliters dose of liposomes. In summary, clodronate-containing liposomes killed testicular macrophages at a far smaller dose than required to kill Leydig cells. Most importantly, neither liposomes no free clodronate had a direct effect on testosterone production. Thus, clodronate-containing liposomes represent a valuable tool to study Leydig cell-macrophage interactions.

Analgesics, Non-Narcotic↗
PubMed1996

The sigma receptor ligand, reduced haloperidol, induces apoptosis and increases intracellular-free calcium levels [Ca2+]i in colon and mammary adenocarcinoma cells.

The sigma receptor ligand reduced haloperidol (50 and 100 microM), potently inhibited cell proliferation, and induced apoptosis in WIDr colon and MCF-7 adenocarcinoma cell lines. Apoptosis was confirmed after drug treatment of the cells by the presence of nuclear fragmentation after staining of the cells with Hoechst 33258 and cellular DNA fragmentation ELISA and by condensation of the heterochromatin using transmission electron microscopy. However, internucleosomal DNA cleavage was not detected using gel electrophoresis. Reduced haloperidol (100 microM) increased the intracellular free calcium levels [Ca2+]i in both cell lines, which was independent of extracellular calcium, suggesting that the rise in [Ca2+]i was from intracellular stores and that an increase in [Ca2+]i may act as a "trigger" for apoptosis in these cell lines.

Adenocarcinoma↗
PubMed1995

A service evaluation of stoma care nurses' practice.

Stoma care nurses aim to meet the physical, psychological, social and spiritual needs of patients. Development of stoma care nursing services has varied, as it has been the responsibility of each nurse, resulting in differences in the mode of delivery. This qualitative and quantitative study involved stoma care nurses from six areas in Essex, to assess patient perception of the service they received. Overall, the satisfaction level was high despite differences in delivery of care especially timing and frequency of visits at home.

Adolescent↗
PubMed1995

Repression of glycoprotein hormone alpha-subunit gene expression and secretion by activin in alpha T3-1 cells.

The alpha T3-1 cell line, a GnRH-responsive gonadotroph cell line developed by targeted oncogenesis in transgenic mice, was used to study regulation of the glycoprotein hormone alpha-subunit by activin. Transient transfection assays established that activin suppressed transcription of both the human and mouse alpha-subunit genes. Initial studies demonstrated that activin decreased transcription of -846 and -180 human alpha-subunit-luciferase constructs by about 30%, but that inhibin and follistatin were without effect. Subsequent studies to localize sequences mediating responses to activin were carried out using a series of 5'-deletions (-507 to -133) of the mouse alpha-subunit promoter fused to luciferase. The luciferase activity of the -507-base pair construct was decreased by 60-70% in the presence of activin, and follistatin prevented this decrease. There were significant stepwise losses of activin responsiveness when sequences between -507 and -424, -424, and -288, and -288 and -205 base pairs were eliminated. Clustered point mutations of the mouse alpha-subunit gene, shown previously to reduce basal expression and GnRH responsiveness, were tested to further identify sequences mediating activin repression. Constructs containing a mutated (-337 to -330) pituitary glycoprotein hormone basal element (PGBE) showed significant loss of activin responsiveness in the context of both the native promoter (-507 to +46) and a minimal promoter downstream of the -507 to -205 region of the mouse alpha-subunit gene, whereas mutation of sequences (-406 to -399) in the GnRH-response element had no effect. Multimers of the PGBE element (-344 to -300) were insufficient to mediate a full activin response when linked to a minimal promoter. When added together with GnRH to transfected cells, activin abolished the stimulatory effect of GnRH on alpha-transcription. Secretion of free alpha-subunit by alpha T3-1 cells decreased 10-50% after exposure to activin for approximately 20 h, and steady state levels of alpha-subunit messenger RNA (mRNA) decreased by about 20-25% after 24-72 h. As changes in activin sensitivity could modulate its action, activin receptor II mRNA levels were measured by Northern blot hybridization at various times after activin (or inhibin) treatment. The three species of ActRII mRNA present in alpha T3-1 cells (approximately 6, 3, and 0.5 kilobases) were unaffected up to 72 h by these treatments. These observations provide the first demonstration that activin regulates a gonadotropin subunit gene at the level of transcription. Suppression of transcription of the mouse alpha-subunit gene by activin appears to involve several segments of the alpha-promoter, one of which is in the region of the PGBE. Thus, alpha T3-1 cells may provide a favorable system to further identify the DNA sequences and nuclear factors through which activin acts to alter transcription.

Activins↗
PubMed1982

Predictive value of ultrasound measurement in early pregnancy: a randomized controlled trial.

Early fetal biparietal diameter (BPD) measurements were obtained with ultrasound in 1062 women attending for antenatal care; a random half had the results withheld from the obstetricians. Of the 1026 women who were sure of the dates of their last normal menstrual period, 829 (81%) were found to have appropriate biparietal diameter measurements, in 3% the pregnancy was more than 2 weeks further advanced and in 14% more than 2 weeks less than calculated. In 30% of the women whose results were intended to be withheld, the code had to be broken because of clinical concern. There were no differences in fetal outcome (birthweight centile, Apgar score at 1 min and perinatal mortality) in the women whose BPD results were known compared with those whose results were withheld from the obstetrician. But a significantly larger number of labours were induced for suspected growth retardation when the gestational age was known.

Clinical Trials as Topic↗
PubMed1980

Results of closed compression capsulotomy for treatment of contracted breast implant capsules.

A prospective study of 544 nonsurgical, closed compression capsulotomies performed on 243 patients for rupture of contracted breast capsule, with at least 1 year follow-up after the last closed capsulotomy procedure, is reported. Two-thirds of the 243 patients maintained softness equal to an unoperated breast for a minimum period of 1 year after the last closed compression capsulotomy. The majority of the patients followed in this study developed breast capsular contracture in less than 12 months after augmentation mammaplasty. The time interval for recurrence of capsular contracture after this first closed capsulotomy correlated closely with the length of time for development of capsular contracture after augmentation mammaplasty. Closed compression capsulotomy will relieve most capsule contractures following augmentation mammaplasty; however, multiple closed capsulotomies may be required to maintain soft breasts, and the patient may require surgical capsulotomy. The procedure offers and alternative to additional surgery or accepting firm breasts and is performed with a minimum of morbidity and financial burden.

Breast↗
PubMed1979

One-dose antibiotic prophylaxis against wound infection after appendicectomy: a randomized trial of clindamycin, cefazolin sodium and a placebo.

Two hundred and fifty patients were admitted to a prospective randomized trial of single dosage prophylaxis against wound infection after appendicectomy. There were 12 exclusions, 72 patients received placebo, 81 received 600 mg i.m. clindamycin phosphate and 85 received 1 1 g i.m. cefazolin sodium, the agent being given in the anaesthetic room. Clindamycin produced a significant reduction in the overall rate of wound infection from 33 per cent in the controls to 17 per cent. In cases with a gangrenous or perforated appendix the infection rate in controls was 78 per cent; this was reduced to 44 per cent by a single dose of clindamycin. Cefazolin significantly reduced the number of aerobic organisms isolated from wound infections, but did not significantly reduce the incidence of wound infection. We conclude that anaerobic organisms are more important than faecal aerobic organisms in the pathogenesis of wound infection after appendicectomy.

Adult↗
PubMed1973

Reactions of papain and of low-molecular-weight thiols with some aromatic disulphides. 2,2'-Dipyridyl disulphide as a convenient active-site titrant for papain even in the presence of other thiols.

1. The u.v.-spectral characteristics of 5,5'-dithiobis-(2-nitrobenzoic acid) (Nbs(2)), 2,2'-dipyridyl disulphide (2-Py-S-S-2-Py), 4,4'-dipyridyl disulphide (4-Py-S-S-4-Py), 5-mercapto-2-nitrobenzoic acid (Nbs), 2-thiopyridone (Py-2-SH) and 4-thiopyridone (Py-4-SH) were determined over a wide range of pH and used to calculate their acid dissociation constants. 2. The reactions of l-cysteine, 2-mercaptoethanol and papain with the above-mentioned disulphides were investigated spectrophotometrically in the pH range 2.5-8.5. 3. Under the conditions of concentration used in this study the reactions of both low-molecular-weight thiols with all three disulphides resulted in the stoicheiometric release of the thiol or thione fragments Nbs, Py-2-SH and Py-4-SH at all pH values. The rates of these reactions are considerably faster at pH8 than at pH4, which suggests that the predominant reaction pathway in approximately neutral media is nucleophilic attack of the thiolate ion on the unprotonated disulphide. 4. The reaction of papain with Nbs(2) is markedly reversible in the acid region, and the pH-dependence of the equilibrium constant for this system in the pH range 5-8 at 25 degrees C and I=0.1 is described by: [Formula: see text] 5. Papain reacts with both 2-Py-S-S-2-Py and 4-Py-S-S-4-Py in the pH range 2.5-8.5 to provide release of the thione fragments, stoicheiometric with the thiol content of the enzyme. 6. Whereas the ratios of the second-order rate constant for the reaction at pH4 to that at pH8 for the cysteine-2-Py-S-S-2-Py reaction (k(pH4)/k(pH8)=0.015) and for the papain-4-Py-S-S-4-Py reaction (k(pH4)/k(pH8)=0.06) are less than 1, that for the papain-2-Py-S-S-2-Py reaction is greater than 1 (k(pH4)/k(pH8)=15). 7. This high reactivity of papain has been shown to involve reaction of the thiol group of cysteine-25, the enzyme's only cysteine residue, which is part of its catalytic site. 8. That this rapid and stoicheiometric reaction of the thiol group of native papain is not shown either by low-molecular-weight thiols or by the thiol group of papain after its active conformation has been destroyed by acid or heat denaturation, strongly commends 2-Py-S-S-2-Py as one of the most useful papain active-site titrants discovered to date. This reagent has been shown to allow accurate titration of papain active sites in the presence of up to 10-fold molar excess of l-cysteine and up to 100-fold molar excess of 2-mercaptoethanol.

Benzoates↗