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Biomedical subjects

I Richmond

Publications and source records attributed to I Richmond.

At least 19 recordsLinked to original sources

Localisation of somatostatin and somatostatin receptors in benign and malignant ovarian tumours.

Somatostatin has been identified as having anti-proliferative, anti-angiogenic and pro-apoptotic actions in many tumour systems, and these effects are mediated through a family of five transmembrane G-protein coupled SRIF receptors. Ovarian cancer is the commonest gynaecological malignancy in the UK and maintenance therapy is urgently required. Native somatostatin expression and its receptors sst(1,2,3 and 5) were studied with immunohistochemistry in 63 malignant and 35 benign ovarian tumours of various histological types. Fifty-seven out of 63 (90%) of malignant and 26/35 (74%) benign tumours expressed somatostatin. Receptors sst(1,2,3 and 5) were expressed variably in epithelial, vascular and stromal compartments for both benign and malignant tumours. Somatostatin was found to correlate significantly with stromal sst(1) (P=0.008), epithelial sst(1) (P<0.001), stromal sst(2) (P=0.019), vascular sst(2) (P=0.026), epithelial sst(3) (P=0.026), stromal sst(5) (P=0.013) and vascular sst(5) (P=0.038). Increased expression of native somatostatin correlating with somatostatin receptors in malignant ovarian tumours raises the possibility that either synthetic somatostatin antagonists or receptor agonists may have therapeutic potential.

Adenocarcinoma↗

Somatostatin receptor 2 expression in the human endometrium through the menstrual cycle.

OBJECTIVE: Somatostatin mediates its many inhibitory functions through five G-protein-coupled receptors (sstr1-5); however, it is not known whether somatostatin or its receptors are present in the endometrium. DESIGN: We have used immunohistochemistry on formalin-fixed paraffin-embedded sections of normal human endometrium from the menstrual (n = 6), proliferative (n = 15) and secretory (n = 10) stages of the endometrial cycle to determine the pattern of expression of somatostatin receptor (sstr) subtype 2. In addition, we have used quantitative polymerase chain reaction (PCR) to determine the level of expression of the sstr2 mRNA in 17 samples of normal human endometrium. PATIENTS: Endometrial tissue had been removed from patients undergoing dilation and curettage (D&C) for menorrhagia and had been determined to be normal histologically. MEASUREMENTS: Immunostaining in the epithelium, endothelium and the stroma of the endometrial sections was characterized and was scored positive or negative. The PCR results were analysed using the software provided to standardize the expression of sstr2 against that of constitutively expressed beta-glucoronidase in the same sample. A final percentage value of the level of sstr2 expression was then determined. RESULTS: sstr2 was expressed variably throughout all the stages of the menstrual cycle in the epithelium, the endothelium and the stroma. In particular, the position of sstr2 expression varied in the epithelial cells surrounding the endometrial glands from being basal or diffuse in the proliferative and secretory phase to being lumenal in the menstrual stage. Quantitative PCR showed that 15 of 17 samples expressed sstr2 mRNA and the level of expression between individual samples varied dramatically. CONCLUSIONS: These data show that sstr2 is present in the endometrium and its location seems to vary through the menstrual cycle.

Adult↗

Errors in the measurement of endometrial depth using transvaginal sonography in postmenopausal women on tamoxifen: random error is reduced using saline instillation sonography.

OBJECTIVE: The endometrium in women on tamoxifen is often made irregular by small cysts. The aim of this study was to assess the accuracy and precision of the measurement of endometrial depth by transvaginal sonography. METHODS: The endometrial depth from endometrial biopsies obtained with the resectoscope in 15 women receiving tamoxifen was compared to the endometrial depth measured by TVS. The inter-observer variability was measured in 58 women. RESULTS: In those biopsies of sufficient quality to allow a measurement, the corresponding depth measurement obtained by ultrasound was up to 3 mm greater than the histological measurement. The interobserver variability for the measurement of endometrial depth using TVS was assessed in 58 postmenopausal women on tamoxifen. The interobserver variability deteriorated as the mean endometrial depth increased, probably because the increase in depth resulted from greater morphological changes within the endometrium such as cyst formation which resulted in an irregular endometrial/myometrial boundary. This may, however, be improved by performing saline instillation sonography. In a prospective study of 10 postmenopausal women, the interobserver variability was significantly greater during tamoxifen treatment compared to pretreatment. CONCLUSIONS: On the basis of the above, if uterine surveillance using TVS were to be offered to postmenopausal women on tamoxifen, then the procedure should be augmented by saline instillation sonography if the endometrial depth is > 4 mm, as this will improve the measurement precision and also identify intrauterine pathology.

Antineoplastic Agents, Hormonal↗

Fatal methane and cyanide poisoning as a result of handling industrial fish: a case report and review of the literature.

The potential health hazards of handling industrial fish are well documented. Wet fish in storage consume oxygen and produce poisonous gases as they spoil. In addition to oxygen depletion, various noxious agents have been demonstrated in association with spoilage including carbon dioxide, sulphur dioxide, and ammonia. A fatal case of methane and cyanide poisoning among a group of deep sea trawler men is described. Subsequent independent investigation as a result of this case led to the discovery of cyanides as a further potential noxious agent. This is thus the first case in which cyanide poisoning has been recognised as a potentially fatal complication of handling spoiled fish. The previous literature is reviewed and the implications of the current case are discussed.

Animals↗

Histological analysis of the uterine junctional zone as seen by transvaginal ultrasound.

OBJECTIVE: This study aimed to investigate the histology of the subendometrial halo, the junctional zone between the endometrium and myometrium. METHODS: Thirteen ex vivo uteri removed for treatment of menorrhagia were studied. In each case, the subendometrial halo, as seen by transvaginal ultrasound, was marked using a Nottingham breast location biopsy needle. A standard histological examination was performed. Full thickness blocks of the anterior uterine wall were taken and standard serial 5-micron tissue sections were prepared from each block. Subsequent morphometric analysis followed staining with Feulgen reagent, using a CAS 200D quantitative image analysis system. Additionally, anti-CD31, an antibody stain for vascular endothelium, was used. RESULTS: The histological examination showed the subendometrial halo to consist of apparently normal myometrium. Morphometric analysis demonstrated a greater total nuclear area in the subendometrial halo than the outer myometrium, but no difference in individual nuclear size between the two zones. CD31 stained a greater total area in the inner myometrium. CONCLUSIONS: These results suggest that the subendometrial halo is a distinct compartment of the myometrium comprising tightly packed muscle cells with an increased vascularity. Such architecture would increase the density of this tissue layer, altering its acoustic impedance, and account for its echopenic appearance on ultrasound.

Adult↗

Least restrictive alternatives: do they really work?

Seclusion and restraint continue to spark debate regarding their therapeutic value and ethical, legal, and humanitarian implications, yet they remain frequently used forms of treatment in psychiatric settings. Identifying specific alternatives to seclusion and restraint use, teaching nursing staff how and when to use them, and determining their effect on patient outcome are important quality improvement issues. A quality improvement study conducted at a long-term care psychiatric facility identified alternatives that nursing staff used and their effect on reducing seclusion and restraint rates. A total of 773 incidents of disruptive behavior were managed with least restrictive alternatives and did not require the use of seclusion or restraint. One-to-one verbal intervention followed by medication as needed represented the most frequently used alternative. Total seclusion and restraint hours decreased by 31 percent, and restraint hours decreased by 47 percent.

Colorado↗

Intrasubject variability in airway inflammation in biopsies in mild to moderate stable asthma.

We have studied intrasubject variability with respect to counts of immunostained inflammatory cells in snap frozen endobronchial biopsies from a group of patients with clinically mild to moderate stable asthma. Fiberoptic bronchoscopy was used to obtain endobronchial biopsies from the upper and lower lobes in 12 volunteer subjects with asthma on two separate occasions 1 mo apart. During this period there was no significant change in asthma treatment, symptom scores, pulmonary function, or airway hyperresponsiveness. With the aid of immunohistochemistry and interactive image analysis, subepithelial counts for T lymphocytes, T-lymphocyte subsets, and eosinophils were made. There was wide intrasubject variability between anatomic site and with time for all the inflammatory cell counts. In each case the intrasubject variability with time was greater than lobar differences. Power calculations were made to establish the optimal sample size required for each marker. We conclude that even in stable asthma considerable biologic variability compounds sampling variability. Such sources of variability need to be borne in mind when calculating the likely power of intervention studies using biopsy data as end points. Power calculations suggest that approximately 15 subjects would be an optimal number with little advantage in increasing beyond this.

Adolescent↗

The customer is always right: patients' perceptions of psychiatric nursing actions.

In this age of consumerism, consideration should be given to patients' perceptions of interactions with the health care provider as a factor in assessing the quality of care provided. This article describes a study of 100 psychiatric inpatients in a large urban medical center who evaluated 50 commonly used psychiatric nursing actions. Significant differences were found between the general psychiatric patient population and the substance abuse population in perception of helpfulness and frequency of performance with 7 of the 50 nursing actions. As the consumer's perception of the effectiveness of nursing actions is determined, emphasis can be given to those interventions when planning patient care.

Adult↗

Effect of high dose inhaled fluticasone propionate on airway inflammation in asthma.

Inhaled corticosteroids are now first-line therapy for most patients with asthma. However, it has been shown that there is ongoing airway inflammation and airway hyperresponsiveness even in the presence of low dose inhaled corticosteroids. To ensure a maximal therapeutic potential we investigated the effect of 3 mo of a very high dose of a new inhaled corticosteroid, fluticasone propionate (FP) (equivalent to 4,000 micrograms daily of beclomethasone dipropionate [BDP]. Twenty asthmatics with mild-to-moderate disease were recruited into this single-blind study. Baseline data were compared with those from 26 normal subjects. Differences in inflammatory indices between asthmatics and normal subjects were detected in both BAL and endobronchial biopsies. After the FP treatment period there was a significant improvement in symptom scores, lung function, and airway responsiveness by a mean 2.8 doubling dilutions of methacholine. Reduction in the airway lymphocyte load and lymphocyte activation was demonstrated and is likely to be an important mechanism mediating the effects of inhaled corticosteroids. Decreased mast cell numbers and activity in atopic asthma suggest that corticosteroids may have additional targets in different types of asthma. Reduced lymphocyte and mast cell activity was found with high dose FP even in those receiving low dose maintenance BDP prior to the study, suggesting a dose-response effect of inhaled corticosteroids on airway inflammation. BAL eosinophilia was still present after FP, indicative of a component of asthmatic airway inflammation that is relatively resistant to corticosteroid therapy.

Administration, Inhalation↗

Distribution of gamma delta T-cells in the bronchial tree of smokers and non-smokers.

AIMS: To assess the distribution of gamma delta T-cells in the human bronchial tree; and to compare quantitatively the differences between gamma delta T-cell numbers in different parts of the airway wall in smokers and non-smokers. METHODS: Full thickness bronchial wall sections were taken from 10 whole lung specimens from both smokers and non-smokers. Serial cryostat sections stained with the monoclonal antibodies CD3 and TCR delta-1 were examined with the aid of interactive image analysis to assess gamma delta T-cell numbers both in absolute terms and as a proportion of total T lymphocyte numbers. RESULTS: In all cases gamma delta T-cells were demonstrable throughout the airway wall. Although in absolute terms they tend to occur predominantly in the bronchial epithelium, this seems to reflect higher numbers of T lymphocytes in the epithelium in general compared with the submucosa. No genuine epitheliotropism is evident. Comparison by smoking status shows a significant increase in gamma delta T-cell numbers in the bronchial glands of smokers compared with non-smokers. CONCLUSIONS: gamma delta T-cells form an integral though variable component of the immunocompetent cell population of the human airway in both smokers and non-smokers. Although epitheliotropism does not exist in the bronchial tree, gamma delta T-cells seem to form a significant part of the bronchial gland inflammation associated with smoking.

Adolescent↗

Bronchus associated lymphoid tissue (BALT) in human lung: its distribution in smokers and non-smokers.

BACKGROUND: Bronchus associated lymphoid tissue (BALT) is a normal component of the lung's immune system in many animals and may be analogous to gut associated lymphoid tissue (GALT). This study aimed at assessing the nature and extent of BALT in human lung and determining whether its expression is induced within the human airway in response to smoking. METHODS: Paraffin embedded, formalin fixed full thickness bronchial wall sections were examined from 31 whole lung specimens derived from both smokers and non-smokers. Samples were taken from throughout the bronchial tree to include main stem bronchi, lobar bronchi and segmental bronchi, as well as first to third generation carinae. Standard 4 microns step sections were stained by haematoxylin and eosin and immunocytochemical methods to show foci of BALT. RESULTS: Examination of 256 airway sites detected 46 foci of BALT. These differed from those described in other mammals in being distributed throughout the bronchial tree, in being found in relation to bronchial glandular epithelium as well as luminal bronchial epithelium, and in lacking any accompanying M cells. Analysis by smoking status showed that the expression of BALT was significantly more common in smokers than non-smokers (82% (14/17) v 14% (2/14) respectively). CONCLUSIONS: The findings support the view that BALT in humans is an integral feature in a comparatively small proportion of lungs from non-smokers while being significantly more prominent in lungs from smokers. The tissue shows several important differences from that described in other mammals.

Adolescent↗

Cytoskeletal filaments in the smooth muscle cells of uterine leiomyomata and myometrium: an ultrastructural and immunohistochemical analysis.

The filamentous components of the cytoskeleton in smooth muscle cells of leiomyomata and normal myometrium were studied by immunohistochemistry and electron microscopy. Fourteen patients hysterectomised for non-malignant disease provided leiomyomata of conventional histological type and histologically normal myometrium: four samples of fetal myometrium were studied by immunohistochemistry alone. All samples of leiomyoma and myometrium were strongly positive for alpha-smooth muscle actin and desmin, the latter often as paranuclear columns or granules. Vimentin was also stained in most samples but less intensely, while cytokeratin stained in about half the samples with an intensity comparable to that of vimentin. By electron microscopy, myofilaments with focal densities were abundant in both normal myometrium and leiomyomata. Intermediate filaments corresponding to the desmin and vimentin demonstrated by immunohistochemistry were also recognised in a variety of architectural arrangements. At one extreme, comparatively small numbers of filaments were loosely distributed around membranous organelles; at the other, filaments formed conspicuous aggregates, largely excluding other organelles and corresponding to the paranuclear granules seen by immunohistochemistry. A comparison of these findings with those of the literature and comments on the possible significance and origin of these aggregates are provided.

Cytoskeleton↗