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Biomedical subjects

R J Davies

Publications and source records attributed to R J Davies.

At least 19 recordsLinked to original sources
PubMed2006

Immunohistochemical estimation of cell cycle phase in laryngeal neoplasia.

We previously developed an immunohistochemical method for estimating cell cycle state and phase in tissue samples, including biopsies that are too small for flow cytometry. We have used our technique to examine whether primary abnormalities of the cell cycle exist in laryngeal neoplasia. Antibodies against the markers of cell cycle entry, minichromosome maintenance protein-2 (Mcm-2) and Ki67, and putative markers of cell cycle phase, cyclin D1 (G1-phase), cyclin A (S-phase), cyclin B1 (G2-phase) and phosphohistone H3 (Mitosis) were applied to paraffin-embedded sections of normal larynx (n = 8), laryngeal dysplasia (n = 10) and laryngeal squamous cell carcinoma (n = 10). Cells expressing each marker were determined as a percentage of total cells, termed the labelling index (LI), and as a percentage of Mcm-2-positive cells, termed the labelling fraction (LF). The frequency of coexpression of each putative phase marker was investigated by confocal microscopy. There was a correlation between Mcm-2 and Ki67 LIs (rho = 0.93) but Mcm-2 LIs were consistently higher. All cells expressing a phase marker coexpressed Mcm-2, whereas Ki67 was not expressed in a proportion of these cells. The putative phase markers showed little coexpression. Labelling index values increased on progression from normal larynx through laryngeal dysplasia to squamous cell carcinoma for Mcm-2 (P = 0.001), Ki67 (P = 0.0002), cyclin D1 (P = 0.015), cyclin A (P = 0.0001) and cyclin B1 (P = 0.0004). There was no evidence of an increase in the LF for any phase marker. Immunohistochemistry can be used to estimate cell cycle state and phase in laryngeal biopsies. Our data argues against primary cell cycle phase abnormalities in laryngeal neoplasia.

Biomarkers, Tumor↗
PubMed2006

A minimally invasive immunocytochemical approach to early detection of oral squamous cell carcinoma and dysplasia.

Squamous dysplasia of the oral cavity indicates increased risk of progression to squamous cell carcinoma (SCC). An important advance would be the development of a minimally invasive assay for identification of oral SCC and dysplasia. We have investigated the suitability in this context of immunostaining oral smears for minichromosome maintainance proteins (MCMs), sensitive and specific biomarkers of cell cycle entry. Immunohistochemical examination of 66 oral tissue samples showed a greater frequency of Mcm-2 expression in surface layers of moderate/severe dysplasia and SCC compared to benign keratosis/mild dysplasia. Immunocytochemistry for Mcm-2/Mcm-5 was performed on 101 oral smears. Conventional smears included 23 from normal mucosa, benign proliferative disease and mild dysplasia, all of which were MCM negative. Of 52 conventional smears of SCC tissue samples, 18 were inadequate. However, MCM-positive cells were present in 33/34 adequate samples. Of 26 liquid-based cytology smears, 19 out of 20 smears from SCC were adequate and all were MCM positive. Six smears from benign lesions were adequate and MCM negative. We conclude that MCMs are promising markers for early detection of oral SCC and dysplasia, particularly in a liquid-based cytology platform. Detection of MCMs would be amenable to automation and potentially applicable in the developing world. Further studies are now warranted.

Biomarkers, Tumor↗
PubMed2006

Characterizing the decay of ancient Chinese silk fabrics by microbeam synchrotron radiation diffraction.

Scanning synchrotron radiation microdiffraction with an approximately 1 x 1 microm(2) beam has been used as a novel method for characterizing the decay of several T'ang dynasty (618-907 AD) silk fabrics. The crystalline fraction could be visualized based on beta-sheet 210 reflection intensities, extracted by recursive peak fits from several thousand diffraction patterns recorded during mesh scans. The azimuthal width of the 210 reflection, which is related to the orientation distribution of the crystalline domains within nanofibrils and the macroscopic orientation of the fibers traversed by the beam, was found to be sensitive to the overall state of decay of the fabric. The fine structure of the histogram of azimuthal width was related to the fiber hierarchical microstructure and the fabric morphology. SAXS/WAXS analysis supports the assumption of an initial loss of the random chain network with decay. At a subsequent state of aging, decay proceeds into the nanofibrils and the silk fibers break up into even smaller fractions.

Fibroins↗
PubMed2005

Bowel function following insertion of self-expanding metallic stents for palliation of colorectal cancer.

OBJECTIVE: Self-expanding metallic stents (SEMS) are an important addition to the treatment of large bowel obstruction. The aim of this study was firstly to assess bowel function following SEMS placement and secondly to identify any potential factors which might aid in the prediction of technical failure of stent insertion. METHODS: A review of all patients undergoing attempted SEMS placement for palliation of malignant left-sided colorectal obstruction over a four-year period (1st May 2000-30th April 2004) was performed. RESULTS: Twenty-one patients (12 male) with a median age of 76 years (range 48-92 years) were included, 11 with metastatic disease and 10 severe comorbidity. SEMS insertion was technically successful in 16 (76%) of 21 cases. Contrast successfully passed through the obstructing lesion in all 16 cases where SEMS placement was technically successful. It only passed through 1 of 5 cases where stenting was not possible (P = 0.0008, Fisher's Exact test). Complications included colonic perforation (1 case), stent migration (1 case) and tumour ingrowth requiring a second stent (1 case). Median survival after SEMS was 12 months (range 1-30 months), and 9 patients died during follow-up. Median bowel frequency following SEMS was 3.5 times per day (range 1-7). Eight patients always passed a liquid stool, 3 others regularly required laxatives and one further patient with poor function after stenting requested a defunctioning stoma. CONCLUSION: Failure of contrast to pass through the obstructing lesion may predict those cases where stenting will not be technically possible. Median survival following SEMS insertion is encouraging in this series, but bowel function is often poor. Expected bowel function should be discussed fully when consenting patients for a SEMS, particularly those with metastatic disease who are otherwise fit for resectional surgery.

Aged↗
PubMed2004

Increased expression of minichromosome maintenance protein 2 in active inflammatory bowel disease.

OBJECTIVE: Minichromosome maintenance protein 2 (Mcm2) is an accurate indicator of cell cycle entry in tissue samples, but its expression in inflammatory bowel disease (IBD) has not previously been investigated. We have used immunohistochemistry to assess the expression of Mcm2, in comparison to the existing proliferation marker Ki-67, in active IBD and IBD without inflammatory activity. MATERIALS AND METHODS: For this experimental study, sections from colonic biopsy and resection specimens of 48 patients with IBD (5 inactive/quiescent Crohn's disease (CD), 13 active CD, 19 inactive/quiescent ulcerative colitis (UC) and 11 active UC) and 15 normal controls were immunostained with antibodies to Mcm2 and Ki-67. The percentage of immunopositive epithelial nuclei was determined by calculating a labelling index (LI) for entire glands and for gland thirds (superficial, middle and basal). RESULTS: The Mcm2 LI was significantly increased in the superficial third of glands in active vs. inactive/quiescent UC (P < 0.0001) and active vs. inactive/quiescent CD (P = 0.001). The Mcm2 LI was significantly greater than the Ki-67 LI in active IBD, both in entire glands (P < 0.0001) and in the superficial third of glands (UC, P = 0.001; CD, P = 0.0002). Mcm2 LIs for entire glands were significantly higher in UC (all cases) compared to CD (all cases) (P = 0.032). CONCLUSIONS: There is increased cell cycle entry, as indicated by expression of Mcm2 and to a lesser extent Ki-67, in the superficial third of colonic glands in active IBD compared to inactive/quiescent IBD. Detection of Mcm2 may contribute to improved histological assessment of small tissue biopsies and may enable the development of a direct stool-based test for detection of active IBD and potentially for assessment of disease activity.

Cell Cycle Proteins↗
PubMed2004

Reduction in the proportion of patients with colorectal cancer presenting as an emergency following the introduction of fast-track flexible sigmoidoscopy: a three-year prospective observational study.

OBJECTIVE: We established a fast-track flexible sigmoidoscopy service to meet the two-week target for colorectal cancer, and have performed a prospective observational study over three years to assess its impact on the proportion of patients with colorectal cancer presenting as an emergency. METHODS: The fast-track system was established on 1 November 1999 using six screening criteria to select high-risk patients. Data on all high-risk patients referred through the fast-track system and all patients diagnosed with colorectal cancer were recorded prospectively in two time periods: six months before fast-track (1 November 1998 to 30 April 1999, Period 1) and three years following fast-track (1 November 1999 to 31 October 2002, Period 2). RESULTS: In Period 2, 2294 fast-track referrals were received. A total of 635 cases (321 male, 314 female) of colorectal cancer were diagnosed in Period 2 vs. 84 cases (43 male, 41 female) in Period 1. In Period 1, 30 patients with colorectal cancer (35.7% of the total) presented as an emergency vs. 165 patients (25.9%) in Period 2 (P = 0.059, chi(2)test). CONCLUSION: Introduction of a fast-track service to meet the two-week target has resulted in a trend towards fewer emergency presentations with colorectal cancer.

Appointments and Schedules↗
PubMed2003

Aberrant expression of minichromosome maintenance protein-2 and Ki67 in laryngeal squamous epithelial lesions.

Histological classification of laryngeal epithelial lesions is highly subjective, and methods of cytological detection are not well developed. Improved determination of aberrant cell cycle entry may allow increased objectivity in histological assessment and enable the development of less invasive diagnostic cytology tests. Sections of normal larynx (n=10), laryngeal dysplasia (n=20) and laryngeal squamous cell carcinoma (SCC) (n=10) were classified according to the Ljubljana classification and stained for markers of cell cycle entry, minichromosome maintenance protein-2 (Mcm-2) and Ki67. Expression patterns were compared using double labelling confocal microscopy. There was a correlation between Mcm-2 and Ki67 labelling indices (rho=0.93; 95% CI [0.84, 0.97]) and both markers showed increased expression from normal epithelium to SCC (Mcm-2, P=0.001; Ki67, P=0.0002). Importantly, there was minimal expression of Mcm-2 or Ki67 in the most superficial layers of normal larynx and abnormal or atypical hyperplasia, in contrast to carcinoma in situ and SCC. Clusters of Mcm-2/5-positive cells were present in cytological preparations from SCC, but not from those showing atypical hyperplasia or inflammation in non-neoplastic tissue. Minichromosome maintenance protein-2 staining may increase the objectivity and reliability of histological grading of laryngeal epithelial lesions. Laryngeal brushings, combined with immuno-enhanced liquid-based cytology, could be useful, as a less invasive approach, to the detection of laryngeal malignant and premalignant lesions.

Antigens, Neoplasm↗
PubMed2003

Androgen and oestrogen receptor status of the human appendix testis.

Since the human appendix testis is a Mullerian duct derivative it has been theorised that rising oestrogen levels in puberty result in enlargement of this organ and consequent predisposition to torsion. This study sought to establish the presence or absence of both androgen and oestrogen receptors in the human appendix testis. Bilateral appendix testis specimens surgically excised from ten patients undergoing scrotal exploration for acute scrotum were stained immunohistochemically for androgen and oestrogen receptors. These were examined by light microscopy. The human appendix testis was found to express both oestrogen and androgen receptors. Marked regional variation of androgen and oestrogen receptor positivity was demonstrated. The surface epithelium and some stromal cells were androgen receptor positive, whereas oestrogen receptors were confined to ductular invaginations, gland-like structures and some stromal cells. Rising levels of androgens and oestrogens in pubertal boys may account for enlargement and the predisposition of the human appendix testis for torsion since this structure contains receptors for both.

Adolescent↗
PubMed2002

Laparoscopic Roux-en-Y gastric bypass: defining the learning curve.

BACKGROUND: Increasing numbers of laparoscopic surgeons are performing laparoscopic Roux-en-Y gastric bypass (LGB). Our aim was to determine the length of the learning curve for a skilled laparoscopic surgeon. METHODS: The study population consisted of the first 225 consecutive LGB procedures attempted by one laparoscopic surgeon (HJS). Outcome parameters included mortality, morbidity, operative time, and conversion to an open procedure. RESULTS: Average operative time decreased from 189 min (first 75 patients) to 125 minutes (last 75 patients). Most of the improvement in operative time occurred over the first 75 patients. The perioperative complication rate decreased from 32% (first 75 patients) to 15% (second and third groups of 75 patients). Complication rates did not significantly decrease after the first 75 patients. Low mortality and conversion rates were achieved early in the series. CONCLUSION: Low mortality rates and low conversion rates can be achieved early in the learning curve for LGB. Complication rates plateau after approximately 75 LGBs, and operative times decrease substantially over the initial 75 cases. Operative times continue to decrease at a slower rate beyond 75 cases.

Adult↗
PubMed2001

Case control study of cerebrovascular damage defined by magnetic resonance imaging in patients with OSA and normal matched control subjects.

STUDY OBJECTIVES: To assess whether MRI detectable evidence of silent cerebrovascular disease is more prevalent in patients with obstructive sleep apnea (OSA) when compared to carefully matched control subjects. DESIGN AND SETTING: Case-control study of patients with OSA attending a specialist sleep clinic and matched control subjects drawn from the normal community. PARTICIPANTS: Forty-five sleep clinic patients with moderate to severe OSA and excessive daytime sleepiness, matched to 45 control subjects without excessive sleepiness or evidence of OSA on a sleep study. Matched variables included age, body mass index (BMI), alcohol and cigarette consumption, treated hypertension, and ischaemic heart disease. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: All subjects underwent 24-hour ambulatory blood pressure recordings (before treatment in OSA patients) and sagittal T1, axial T2, and coronal dual echo cerebral MRI imaging to detect clinically silent abnormalities related to hypertensive cerebrovascular disease; areas of high signal foci in deep white matter (DWM), lacunae, and periventricular hyperintensity. Lacunae/high signal foci in DWM and/or periventricular hyperintensity were present in 15 (33%) OSA subjects and 16 (35%) controls, despite significant increases in mean daytime diastolic blood pressure (4.6mmHg, p<0.05), and both nighttime diastolic (7.2mmHg, p<0.001) and systolic blood pressures (9.2mmHg, p<0.05) in OSA subjects. These data exclude more than a 17% excess prevalence of MRI detected minor cerebrovascular disease in the OSA patients, with 95% confidence. CONCLUSIONS: Sub-clinical cerebrovascular disease is prevalent in both clinic patients with OSA and their matched control subjects. Despite the increased arterial blood pressures, there is, however, no apparent excess of MRI-evident subclinical cerebrovascular disease in patients with OSA compared to appropriately matched control subjects.

Adult↗
PubMed2001

Laparoscopic wedge resection of a gastric leiomyoma.

Gastric stromal tumors represent a small percentage of gastric neoplasms. Establishing a diagnosis when these lesions are encountered usually is not possible with limited biopsies. Benign and malignant gastric stromal tumors require only local excision for definitive treatment. However, most lesions are not amenable to endoscopic excision. As a result, laparoscopic local excision offers the ideal method to establish a diagnosis and to treat patients with gastric smooth muscle tumors. We present a minimally invasive local excision of a gastric stromal tumor. We also review the previously published management of gastric stromal tumors and show how it is being influenced by laparoscopy.

Female↗
PubMed2001

Is (re)titration of nasal continuous positive airway pressure for obstructive sleep apnoea necessary?

OBJECTIVE: To assess changes in nasal continuous positive airway pressure (nCPAP) pressure requirements across time in obstructive sleep apnoea (OSA), and whether routine retitrations are indicated. BACKGROUND: Most sleep laboratories perform one nCPAP titration, although some authors have found changes in pressures with time. A cohort of patients with OSA in a randomised controlled trial of nCPAP provided us with data on changes in titration pressures with time. METHODS: One hundred and one patients with symptomatic OSA (Epworth Sleepiness Scale > or =10, and >10 episodes/h of >4% dips in SaO(2) overnight) were recruited to a 1 month trial comparing real (autotitrated) and placebo nCPAP. At 1 month all patients were titrated and received real nCPAP thereafter. Eighty five were retitrated at about 6 months. RESULTS: Average pressures did not change between the initial value and 1 month (95th centile, 8.47 (SD 3.00), 8.94 (2.85) cm H(2)O), although there were large individual changes (mean difference, +0.47, SD 2.30, range -5 to +6 cm H(2)O). There was a small fall at 6 months (mean difference -0.68, SD 2.60, range -6 to +6 cm H(2)O, P<0.03) with no suggestion that the changes from 1-6 months were clinically important. CONCLUSIONS: This study suggests that routine nCPAP retitrations are not necessary. In conjunction with other published data, the night to night variation we found implies that a nCPAP calibration using an algorithm (based on obesity and OSA severity) might be as clinically successful as conventional one night titrations. However, further studies will be needed to specifically confirm this hypothesis.

Clinical Trial↗
PubMed2001

Interaction of cigarette smoke and house dust mite allergens on inflammatory mediator release from primary cultures of human bronchial epithelial cells.

Several studies have shown that exposure to cigarette smoke and/or house dust mite (HDM) can lead to increased airway inflammation in susceptible individuals. The underlying mechanisms, however, are not defined. To investigate the interaction between cigarette smoke and HDM allergen on mediator release from primary cultures of human bronchial epithelial cells. Confluent human bronchial epithelial cell cultures were exposed to cigarette smoke in the absence or presence of HDM allergen and investigated for the release of IL-8, IL-1beta, and sICAM-1. Damage to the epithelial cells themselves was assessed by release of 51Cr. On separate occasions, we investigated the effect of PTL11028, a highly potent and selective Der p1 inhibitor, on HDM allergen-induced release of IL-8, following activation of HDM allergen by incubation with cysteine. The effect of cigarette smoke exposure on the stability of these released mediators in prepared solutions in the absence/presence of reduced glutathione was also studied. Both HDM allergens and short-term (20 min) cigarette smoke exposure led to a significantly increased release of IL-8, IL-1beta and sICAM-1 from the epithelial cell cultures. Longer exposure (1-6 h) to cigarette smoke led to a dramatic decrease in the amount of these mediators detected in the culture medium. Whilst incubation of epithelial cultures with HDM allergen did not cause any significant change in the release of 51Cr from pre-loaded cells, cigarette smoke on its own led to a marked, exposure and incubation-time dependent increase in the release of 51Cr. Incubation with HDM allergen led to a significant, dose and time-dependent increase in the release of IL-8, which was further enhanced when the allergen extract was pre-activated with cysteine. This effect was completely abrogated by PTL11028, a novel Der p1 inhibitor. Prepared solutions of various concentrations of IL-8, IL-1beta and sICAM-1 exposed to cigarette smoke demonstrated a dramatic exposure time-dependent decrease in the detectable amount of these mediators, an effect which was abrogated by GSH. HDM-induced airway inflammation may include Der p-mediated release of inflammatory mediators from epithelial cells. Additionally, short-term cigarette smoke exposure may induce airway inflammation by release of inflammatory mediators from these cells, an effect which may be potentiated by Der p allergens. Longer term cigarette smoke exposure may cause damage to epithelial cells and changes in the structure of inflammatory mediators.

Aged↗