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Biomedical subjects

M Morgan

Publications and source records attributed to M Morgan.

At least 37 records · Page 2Linked to original sources
PubMed2004

Botulinum toxin: helpful adjunct to early resolution of laryngeal granulomas.

Treating laryngopharyngeal reflux is the most accepted treatment for laryngeal granulomas. However, response to this treatment is prolonged and in some cases persistent. The authors hypothesize that this is due to the continuous trauma to the mucoperichondrium from adduction of the vocal folds thus preventing regeneration of healthy mucosa. A prospective study was performed on six patients with laryngeal granulomas failing prolonged laryngopharyngeal reflux treatment, speech therapy, and surgical excisions. Botulinum toxin A was injected into the affected thyroarytenoid to reduce adduction trauma. Video-stroboscopy was used to assess response. A 50 per cent reduction in the size of the granulomas was noted within two weeks with a complete and permanent response within two to eight weeks in five out of six patients. One patient had an obstructing pyogenic granuloma that required excision and recurred after excision but responded to a repeated injection. The addition of a single injection of botulinum toxin A to the standard treatment expeditiously eliminated persistent and recurrent laryngeal granulomas.

Aged↗
PubMed2003

Genetic contributions to generalized arousal of brain and behavior.

We have identified a generalized arousal component in the behavior of mice. Analyzed by mathematical/statistical approaches across experiments, investigators, and mouse populations, it accounts for about 1/3 of the variance in arousal-related measures. Knockout of the gene coding for the classical estrogen receptor (ER-alpha), a ligand-activated transcription factor, greatly reduced arousal responses. In contrast, disrupting the gene for a likely gene duplication product, ER-beta, did not have these effects. A combination of mathematical and genetic approaches to arousal in an experimentally tractable mammal opens up analysis of a CNS function of considerable theoretical and practical significance.

Animals↗
PubMed2003

Growth hormone secretagogue receptors in rat and human gastrointestinal tract and the effects of ghrelin.

The peptide hormone ghrelin is known to be present within stomach and, to a lesser extent, elsewhere in gut. Although reports suggest that gastric function may be modulated by ghrelin acting via the vagus nerve, the gastrointestinal distribution and functions of its receptor, the growth hormone secretagogue receptor (GHS-R), are not clear and may show signs of species-dependency. This study sought to determine the cellular localisation and distribution of GHS-R-immunoreactivity (-Ir) using immunofluorescent histochemistry and explore the function of ghrelin in both human and rat isolated gastric and/or colonic circular muscle preparations in which nerve-mediated responses were evoked by electrical field stimulation. The expression of GHS-R-Ir differed to a greater extent between species than between gut regions of the same species. Both the human and rat gastric and colonic preparations (n=3 each) expressed GHS-R-Ir within neuronal cell bodies and fibres, cells associated with gastric glands and putative entero-endocrine and/or mast cells. Smooth muscle cells and epithelia were devoid of GHS-R-Ir and only rat preparations expressed GHS-R-Ir on nerve fibres associated with the muscle layers. GHS-R-Ir was fully competed in all cases in pre-adsorption studies and antiserum specificity was confirmed using a cell line transiently expressing the rat GHS-R. In rat isolated forestomach circular muscle, ghrelin 0.1-10 microM had no effect on smooth muscle tension but concentration-dependently facilitated the amplitude of contractions evoked by excitatory nerve stimulation (n=4-7; P<0.05 for each concentration versus vehicle; n=18). When examined under similar conditions, in both rat distal colon (n=4-6, P>0.05 each) and human ascending (n=3) and sigmoid (n=1) colon, these concentrations of ghrelin were without effect (P>0.05 each). The data suggest that ghrelin has the potential to profoundly affect gastrointestinal functions in both species and at least one of these functions is to exert a gastric prokinetic activity. Moreover, we suggest that this activity of ghrelin is mediated via the enteric nervous system, in addition to known vagus nerve-dependent mechanisms.

Animals↗
PubMed2003

How can a nurse intervention help people with newly diagnosed epilepsy? A qualitative study of patients' views.

The aim was to describe the patients' views of the challenges posed by a new diagnosis of epilepsy and their assessment of a nurse intervention. Neurologists in South-East England referred patients into the study. Following a trial of a nurse intervention a subgroup of patients were purposefully identified for in depth interviews. Transcriptions of tape-recorded interviews were analysed using qualitative methodology. We found that younger people with epilepsy seemed to experience more trouble with driving, jobs and managing their lives in the context of new epilepsy, while older people saw epilepsy as just another illness to cope with. Patients reported difficulty in remembering what their doctors told them which they attributed partly to lack of time available in the consultation. They valued the time, and the technique of probing with explanations used by the nurse. The nurse intervention was seen as useful in making sense of symptoms, tests, risk management, and driving regulations and in helping manage their medicine taking. We conclude that people with newly diagnosed epilepsy face different challenges, some of which are related to their age at diagnosis. Patients reported help from the nurse with understanding the diagnosis, tests, risk management and taking their medication. Follow-up is necessary to measure behavioural effects on self-management in the long-run.

Adolescent↗
PubMed2003

High molecular weight cytokeratin antibody (clone 34betaE12): a sensitive marker for differentiation of high-grade invasive urothelial carcinoma from prostate cancer.

AIMS: There is no well-established positive immunomarker for urothelial carcinoma. We evaluated the diagnostic utility of high molecular weight cytokeratin (HMWCK) antibody clone 34betaE12 in differentiating high-grade invasive urothelial carcinoma from prostate cancer. METHODS AND RESULTS: Formalin-fixed paraffin-embedded sections from 28 cases of high-grade invasive urothelial carcinoma (20 not otherwise specified (UC-NOS), eight with glandular differentiation) and 20 cases of poorly differentiated prostate carcinoma were immunostained with a monoclonal antibody to carcinoembryonic antigen (CEA), clone 85A12 and with HMWCK antibody clone 34betaE12 after microwave pretreatment or protease 24 predigestion. All cases of UC-NOS expressed HMWCK on 34betaE12 immunostaining after microwaving or enzyme predigestion. Immunoreactivity was intense and diffuse in all the cases after microwave pretreatment, whilst with enzyme predigestion immunoreactivity was sometimes patchy with <50% tumour cells positive in 20% of cases. In comparison with 34betaE12, 85A12 was insensitive with 15% of UC-NOS cases totally CEA-negative and <50% tumour cell immunoreactivity in 60% of cases. Rare positive cells were present in two (10%) cases of prostate cancer with monoclonal anti-CEA and 34betaE12 on microwaved sections, but all the cases were HMWCK-negative using 34betaE12 on sections pretreated by enzyme digestion. CONCLUSIONS: HMWCK antibody clone 34betaE12, particularly when used with microwave heat retrieval, is a very sensitive positive marker for high-grade invasive urothelial carcinoma.

Adenocarcinoma↗
PubMed2003

Dental caries experience in a young adult military population.

BACKGROUND: The purpose of this study was to investigate a group of young Australian adults to determine their caries experience and compare these current levels with similar aged cohorts over the past 30 years. Caries experience was also related to lifetime exposure of fluoridated water consumption. METHODS: This was achieved through a cross-sectional study involving Australian Army recruits seen for their initial dental examination at 1st Recruit Training Battalion, Kapooka. A total of 499 recruits had a clinical examination with the aid of bitewing radiographs and an orthopantogram. Sociodemographic and fluoride history data were elicited via a questionnaire. RESULTS: Mean DMFT scores for age cohorts were: 17-20 years of age--DMFT 3.59; 21-25 years of age--DMFT 4.63; 26-30 years of age--DMFT 7.07; 31-35 years of age--DMFT 9.04. Subjects with a lifetime exposure to fluoridated water had significantly lower dental caries experience (DMFT 3.80) than subjects with no exposure to fluoridated water (DMFT 5.15). CONCLUSIONS: It was found that there has been a decline in the level of caries experience in young Australian adults when the data from this study were compared to other ad hoc studies.

Adult↗
PubMed2002

p53 and DCC immunohistochemistry in curative rectal cancer surgery.

BACKGROUND AND AIMS: In rectal cancer altered expression of p53 or DCC may be indicative of poor patient prognosis. This study determined by immunohistochemistry the tumour status of p53 protein and DCC protein in patients with rectal cancer who had a curative resection and were followed-up prospectively and examined the correlation to clinical and pathology variables. PATIENTS AND METHODS: The study included 171 who had a curative resection for rectal cancer: 88 at Concord Hospital (CH) followed up for a mean of 11 years and 83 at Royal Prince Alfred Hospital (RPAH) followed up prospectively for a mean of 4.3 years. Specimens were assessed by immunohistochemical assay of p53 expression ( n=170) and of DCC expression ( n=168). RESULTS: p53 over-expression was demonstrated in 58% of CH tumours and 59% of RPAH tumours. Absence of normal DCC expression was demonstrated in 66% of CH tumours and 52% of RPAH tumours. On both separate and combined analysis of these groups there were no significant associations by univariate analysis between p53 expression or DCC expression or combinations of p53 and DCC expression and the pathology variables: extent of penetration through bowel wall, lymph node involvement, presence of venous invasion, and tumour differentiation. CONCLUSION: The immunohistochemical p53 and DCC status of rectal tumours was not associated with other clinical or pathology variables, nor predictive of outcome.

Cell Adhesion Molecules↗
PubMed2002

Efficacy of vaccination with plasmid DNA encoding for HER2/neu or HER2/neu-eGFP fusion protein against prostate cancer in rats.

Despite early diagnosis and improved therapy, 31,500 men will die from prostate cancer (PC) this year. The HER2/neu oncoprotein is an important effector of cell growth found in the majority of high-grade prostatic tumors and is capable of rendering immunogenicity. The antigenicity of this oncoprotein might prove useful in the development of PC vaccines. Our goal is to prove the principle that a single DNA vaccine can provide reliable immunity against PC in the MatLyLu (MLL) translational tumor model. The parental rat MatLyLu PC cell line expresses low to moderate levels of the rat neu protein. To simulate in vivo human PC, MatLyLu cells were transfected with a truncated sequence of human HER2/neu cDNA cloned into the pCI-neo vector. This HER2/neu cDNA sequence encodes the first 433 amino acids of the extracellular domain (ECD). MatLyLu cells were also transfected with the same HER2/neu cDNA sequence cloned into the N1-terminal sequence of EGFP reporter gene to produce a fusion protein. The partial ECD sequence of HER2/neu includes five rat major histocompatibility (MHC)-II-restricted peptides with complete human-to-rat cross-species homology. The HER2/neu protein overexpression was documented by Western Blot analysis, and the expression of fusion protein was monitored by confocal microscopy and fluorimetry. Vaccination with a single injection of HER2/neu cDNA protected 50% of animals against HER2/neu-MatLyLu tumors (P < 0.01). When the tumor cells were engineered to express HER2/neu-EGFP fusion protein, the antitumor immunity was enhanced, as following vaccination with HER2/neu-EGFP cDNA, 80% of these rats rejected HER2/neu-EGFP-MatLyLu (P<0.001). Both vaccines induced HER2/neu-specific antibody titers. Rats vaccinated with EGFP-cDNA rejected 80% of EGFP-MatLyLu tumors and, interestingly, 40% of HER2/neu-MatLyLu tumors. None of the cDNA vaccines induced immunity against parental MatLyLu cells. Our data clearly demonstrate that a single injection of HER2/neu-EGFP cDNA is a very effective vaccine against PC tumors expressing the cognate tumor-associated antigen (TA). The antitumor immunity is significantly more pronounced if the tumors express xenogeneic HER2/neu-EGFP fusion protein as opposed to only the syngeneic HER2/neu oncoprotein. Our data suggests that the HER2/neu-EGFP-MatLyLu tumor is a potential animal tumor model for investigating therapeutic vaccine strategies against PC in vivo and demonstrates the limitations of a cDNA vaccine only encoding for MHC-II-restricted HER2/neu-ECD sequence peptides.

Animals↗
PubMed2002

How can a nurse intervention help people with newly diagnosed epilepsy? A qualitative study (of patients' views).

The aim was to describe the patients' views of the challenges posed by a new diagnosis of epilepsy and their assessment of a nurse intervention. Neurologists in South-East England referred patients into the study. Following a trial of a nurse intervention a subgroup of patients were purposefully identified for in-depth interviews. Transcriptions of tape-recorded interviews were analysed using qualitative methodology. We found that younger people with epilepsy seemed to experience more trouble with driving, jobs and managing their lives in the context of new epilepsy, while older people saw epilepsy as just another illness to cope with. Patients reported difficulty in remembering what their doctors told them which they attributed partly to lack of time available in the consultation. They valued the time, and the technique of probing with explanations used by the nurse. The nurse intervention was seen as useful in making sense of symptoms, tests, risk management, and driving regulations and in helping manage their medicine taking. We conclude that people with newly diagnosed epilepsy face different challenges, some of which are related to their age at diagnosis. Patients reported help from the nurse with understanding the diagnosis, tests, risk management and taking their medication. Follow-up is necessary to measure behavioural effects on self-management in the long run.

Adolescent↗
PubMed2002

A clinicopathologic and immunohistochemical analysis of melanotic neuroectodermal tumor of infancy.

OBJECTIVE: The purpose of this study was to review the features of 8 cases of melanotic neuroectodermal tumor of infancy (MNTI) of the jaws with respect to the expression of NB84, CD99, PGP 9.5, specific cytokeratins, and Ki-67, markers not previously reported in this entity. STUDY DESIGN: A clinicopathologic and immunohistochemical analysis of MNTIs in 8 children was undertaken. RESULTS: Patients were aged 2(1/2) months to 14 months. Seven were males. Seven lesions affected the maxilla. Microscopically, collections of larger, melanocyte-like cells were admixed with smaller, neuroblast-like cells. All MNTIs contained melanin; although most showed cellular atypia, mitoses were infrequent (<2 per 10 high-power fields). However, in one lesion in which the melanocyte-like cells appeared less differentiated, 7 mitoses per 10 high-power fields were counted. The larger cells expressed cytokeratins 7 (4/8), 8 (8/8), 18 (6/8), and 19 (3/8); PGP 9.5; neuron-specific enolase (6/8); S100; HMB45; and chromogranin A (2/8). The small cells expressed CD56 (7/8), neuron-specific enolase (7/8), synaptophysin (3/8), PGP 9.5 (3/8), and chromogranin A (2/8). No MNTIs expressed NB84. The most mitotically active tumor was the only one to show membrane expression of CD99 (by both cell populations), have a detectable Ki-67-positive fraction (25% in both the large- and small-cell components), behave aggressively, and require bilateral maxillectomy. All other MNTIs responded to local excision, and none metastasized. CONCLUSIONS: Most MNTIs are benign and respond to conservative excision. Histology is an unreliable means of predicting clinical behavior, but this study has identified some morphologic and phenotypic features that may indicate a more aggressive lesion.

12E7 Antigen↗
PubMed2002

Prospective study of liver dysfunction in pregnancy in Southwest Wales.

BACKGROUND: Liver dysfunction in pregnancy has serious consequences. Its frequency and characteristics have not been systematically documented in Britain. We have prospectively determined incidence, causes, and outcome of liver dysfunction in pregnancy in an obstetric unit in Southwest Wales, UK. METHODS: A central laboratory identified all abnormal liver tests (bilirubin >25 micro mol/l, aspartate transaminase >40 U/l, or gamma glutamyl transpeptidase >35 U/l) from patients in antenatal clinics and wards of an obstetric unit serving a population of 250 000. Patients with abnormal liver tests were assessed and followed throughout and after pregnancy [corrected]. Medical advice was provided to obstetric teams. FINDINGS: There were 4377 deliveries during the 15 month study. A total of 142 patients had abnormal liver tests. There were 206 contributing diagnoses, the great majority being pregnancy specific. Among the most important were pre-eclampsia (68), HELLP (haemolysis, elevated liver enzymes, low platelets) syndrome (30), obstetric cholestasis (23), hyperemesis gravidarum (11), acute fatty liver of pregnancy (five), and hepatic infarct (one). Sepsis, postoperative factors, and placental pathology (51) were not uncommonly responsible but incidental or pre-existing hepatobiliary disease was infrequent (17). Sixty five patients were delivered early by induction or caesarean section because of liver dysfunction. Despite substantial liver related morbidity, there were no maternal deaths and only two intrauterine deaths. CONCLUSIONS: Liver dysfunction was seen in 3% of deliveries during a 15 month prospective study and was usually directly related to pregnancy with spontaneous recovery in the puerperium. Incidence of the most serious conditions, acute fatty liver of pregnancy and HELLP syndrome, was much greater than previously reported. Profound effects on maternal and infant health were observed but close medical and obstetric collaboration ensured low mortality.

Adult↗
PubMed2002

Pathways to HIV testing and care by black African and white patients in London.

OBJECTIVE: To examine factors associated with uptake of HIV clinic services by black African HIV positive people living in London. DESIGN: Questionnaire survey of patients attending study clinic. SETTING: HIV outpatient clinic in south London, UK. SUBJECTS: All HIV positive patients attending the clinic between July 1999 and March 2000. MAIN OUTCOME MEASURES: Use of health services, delay in seeking HIV test, pre-HIV test concerns, delay in uptake of HIV care, barriers to clinic use, disclosure, sources of support. RESULTS: 392 questionnaires were completed. Respondents were 64% white, 26% black African, and 10% from other ethnic groups. Twenty eight per cent of black Africans suspected they were HIV positive before diagnosis (white patients 45% (p<0.01)). Before testing 11% of black Africans had previously attended a genitourinary medicine clinic, 80% had consulted a GP. Twenty per cent of black Africans expressed concern over entitlement to care and where to get an HIV test. The majority of black Africans (66%) received HIV care within 1 month of their diagnosis. They were significantly (p<0.01) less likely than white patients to disclose their HIV status to family and friends. CONCLUSION: This study suggests that although black Africans are a high risk group for HIV infection they generally do not suspect their status. While they may delay testing, their uptake of HIV clinic care and use of statutory and voluntary support services after diagnosis is similar to their white counterparts. However, they lack informal support networks. This study highlights the continuing need for health promotion work among London's African communities, to reduce the stigma surrounding HIV/AIDS and to raise awareness of the benefits of testing.

Adult↗
PubMed2001

Spatial organization of signal transduction molecules in the NK cell immune synapses during MHC class I-regulated noncytolytic and cytolytic interactions.

The cytolytic activity of NK cells is tightly regulated by inhibitory receptors specific for MHC class I Ags. We have investigated the composition of signal transduction molecules in the supramolecular activation clusters in the MHC class I-regulated cytolytic and noncytolytic NK cell immune synapses. KIR2DL3-positive NK clones that are specifically inhibited in their cytotoxicity by HLA-Cw*0304 and polyclonal human NK cells were used for conjugate formation with target cells that are either protected or are susceptible to NK cell-mediated cytotoxicity. Polarization of talin, microtubule-organizing center, and lysosomes occurred only during cytolytic interactions. The NK immune synapses were analyzed by three-dimensional immunofluorescence microscopy, which showed two distinctly different synaptic organizations in NK cells during cytolytic and noncytolytic interactions. The center of a cytolytic synapse with MHC class I-deficient target is comprised of a complex of signaling molecules including Src homology (SH)2-containing protein tyrosine phosphatase-1 (SHP-1). Closely related molecules with overlapping functions, such as the Syk kinases, SYK, and ZAP-70, and adaptor molecules, SH2 domain-containing leukocyte protein of 76 kDa and B cell linker protein, are expressed in activated NK cells and are all recruited to the center of the cytolytic synapse. In contrast, the noncytolytic synapse contains SHP-1, but is lacking other components of the central supramolecular activation cluster. These findings indicate a functional role for SHP-1 in both the cytolytic and noncytolytic interactions. We also demonstrate, in three-cell conjugates, that a single NK cell forms a cytolytic synapse with a susceptible target cell in the presence of both susceptible and nonsusceptible target cells.

Cell Polarity↗
PubMed2001

Phase III, multicenter, double-blind, randomized study of letrozole, an aromatase inhibitor, for advanced breast cancer versus megestrol acetate.

PURPOSE: To compare two doses of letrozole (0.5 mg and 2.5 mg every day) and megestrol acetate (40 mg qid) as endocrine therapy in postmenopausal women with advanced breast cancer previously treated with antiestrogens. PATIENTS AND METHODS: This double-blind, randomized, multicenter, multinational study enrolled 602 patients, all of whom were included in the primary analysis in the protocol. Patients had advanced or metastatic breast cancer with evidence of disease progression while receiving continuous adjuvant antiestrogen therapy, had experienced relapse within 12 months of stopping adjuvant antiestrogen therapy given for at least 6 months, or had experienced disease progression while receiving antiestrogen therapy for advanced disease. Tumors were required to be estrogen receptor- and/or progesterone receptor-positive or of unknown status. Confirmed objective response rate was the primary efficacy variable. Karnofsky Performance Status and European Organization for Research and Treatment of Cancer quality-of-life assessments were collected for 1 year. RESULTS: There were no statistically significant differences among the three treatment groups for overall objective tumor response. Patients treated with letrozole 0.5 mg had improvements in disease progression (P =.044) and a decreased risk of treatment failure (P =.018), compared with patients treated with megestrol acetate. Letrozole 0.5 mg showed a trend (P =.053) for survival benefit when compared with megestrol acetate. Megestrol acetate was more likely to produce weight gain, dyspnea, and vaginal bleeding, and the letrozole groups were more likely to experience headache, hair thinning, and diarrhea. CONCLUSION: Given a favorable tolerability profile, once-daily dosing, and evidence of clinically relevant benefit, letrozole is equivalent to megestrol acetate and should be considered for use as an alternative treatment of advanced breast cancer in postmenopausal women after treatment failure with antiestrogens.

Aged↗
PubMed2001

The minisatellite of the GPI/AMF/NLK/MF gene: interspecies conservation and transcriptional activity.

Minisatellites are tandemly repeated DNA sequences found throughout the genomes of all eukaryotes. They are regions often prone to instability and hence hypervariability; thus repeat unit sequence is generally not conserved beyond closely related species. We have studied the minisatellite located in intron 9 of the human glucose phosphate isomerase (GPI) gene (also known as neuroleukin, autocrine motility factor, maturation and differentiation factor) and have found, by Zoo blotting coupled with PCR amplification and DNA sequencing, that similar repeat units are present in seven other species of mammal. There is also evidence for the presence of the minisatellite in chicken. The repeat unit does not appear to be present at any other locus in these genomes. Minisatellite DNA has been reported to be involved in recombination activity, control of gene expression of nearby gene(s) (both transcriptional and translational), whilst others form protein coding regions. The high level of conservation exhibited by the GPI minisatellite, coupled with the unique location, strongly suggests a functional role. Our results from transient and stable transfections using luciferase reporter constructs have shown that the GPI minisatellite region can act to increase transcription from the SV40 promoter, CMV promoter and the human GPI promoter.

Animals↗
PubMed2001

Comparison of self-report, video observation and direct measurement methods for upper extremity musculoskeletal disorder physical risk factors.

The prevention of work-related musculoskeletal disorders has become a national priority in many countries. Increasingly, attempts are made to quantify those exposures that increase risk in order to set exposure limit values. This study used commonly employed field measurement methods and tools in order to perform an inter-method comparison between three primary methods of risk factor exposure assessment: self-report questionnaires, observational video analysis and direct measurement. Extreme posture duration, repetition, hand force (estimated from electromyography) and movement velocity were assessed for 18 subjects while performing each of three jobs processing tree seedlings. Results indicated that self-reports were the least precise assessment method, which consistently overestimated exposures for each of the measured risk factors. However, adjustment of the reports as psychophysical scales may increase agreement on a group level. Wrist flexion/extension duration and repetition were best measured by electrogoniometer. Electrogoniometric measures of wrist deviation duration and frequency were less precise than video analysis. Forearm rotation duration and repetition, grip force and velocity appeared to be best quantified by direct measurement as measured by electrogoniometer and electromyography (EMG) (as root-mean-square amplitude). The results highlight the fact that it is as important to consider and report estimated measurement error in order to reduce potential exposure misclassification in epidemiologic studies.

Arm↗