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Biomedical subjects

M Wells

Publications and source records attributed to M Wells.

At least 55 records · Page 3Linked to original sources
PubMed1999

CD44 is a marker of endocervical neoplasia.

The expression of CD44s, CD44v4, CD44v5, CD44v7-8, and CD44v10 was investigated immunohistochemically in a variety of neoplastic cervical lesions. Normal endocervical columnar cells exhibited no reactivity for any of the antibodies, whereas the subcolumnar reserve cells were strongly positive for CD44s, CD44v5, and CD44v7-8. In some cases, positive cells were identified in the stroma surrounding the endocervical glands and adjacent to reserve cells. Cervical glandular intraepithelial neoplasia and adenocarcinoma showed consistent immunoreactivity for CD44v5. There was no significant change in CD44 immunoreactivity in squamous cell carcinoma compared with normal epithelia and cervical intraepithelial neoplasia. These findings lend support to the origin of carcinoma of the cervix from a common progenitor reserve cell and suggest the origin of reserve cells from the stroma. CD44v5 may be useful as a diagnostic marker of endocervical neoplasia and could provide a target for therapeutic approaches directed against specific epitopes.

Adenocarcinoma↗
PubMed1999

Menopausal changes in the myometrium: an investigation using a GnRH agonist model.

Thirty-four premenopausal women were randomized to receive 3.75 mg of leuprorelin acetate depot or placebo for 8 weeks before hysterectomy. Postoperatively, the myometrium was examined by two independent pathologists and the pathologic features were graded. Computer analysis was used to assess myometrial cellularity and arterial wall structure (on hematoxylin and eosin-stained sections) and vascularity (on sections immunostained for Factor VIII-related antigen). The cellularity of the gonadotrophin-releasing hormone agonist-treated myometrium was higher than the controls with less stromal edema. Focal myometrial hyalinization was present in a minority of cases, all in the gonadotrophin-releasing hormone agonist-treated cases. The arteries in the gonadotrophin-releasing hormone agonist-treated uteri underwent atrophy of the tunica media and had significantly more perivascular fibrosis. The number of vessels per 100 myocytes also was decreased. Hypoestrinism secondary to leuprorelin treatment leads to myocyte atrophy, decreased stromal edema, atrophy of the arcuate arteries, and decreased myometrial vascularity.

Arteries↗
PubMed1999

Observed behaviors of patients with probable Alzheimer's disease who are hospitalized for diagnostic tests.

This study examines observed behaviors of hospitalized patients with probable Alzheimer's disease (AD) undergoing invasive diagnostic procedures. Data was obtained from nursing documentation in the medical records of 30 patients, 10 in each stage of AD (i.e., mild, moderate, severe). In general, analysis of the data revealed that changes in behavior occurred immediately prior to, during, and following these procedures. Specifically, the moderately impaired patients showed the most significant curve over the 5-day observation period, while patients in the mildly impaired group showed a high peak of behavioral change on the test day. The severely impaired group of patients had a higher sustained level of activity throughout the 5-day period. Routine assessment of the patients' usual behaviors, care-givers' knowledge of the stage of disease, and awareness of the potential impact that diagnostics may have on cognitively impaired patients could help care providers decide what interventions most likely would lead to successful outcomes.

Aged↗
PubMed1998

Short-term exposures of rats to airborne hydrogen fluoride.

A series of acute inhalation exposures was performed with airborne hydrogen fluoride (HF) to establish the concentration response for nonlethal effects in the rat. Exposures were either 2 or 10 min long; concentrations ranged from 135 to 8621 ppm. Three additional exposures (20 to 48 ppm) were performed for 60 min. A mouth-breathing (MB) model with a tracheal cannula was used in most of the exposures to maximize delivery of the HF to the lower respiratory tract. Endpoints on the day after exposure included hematology, serum chemistry, bronchoalveolar lavage, pulmonary function, organ weights, and histopathology. Nasal resistance was measured in nose-breathing (NB) groups. Effects of exposure were generally limited to the respiratory tract and included alveolitis, bronchial lesions, altered parameters of pulmonary function and bronchoalveolar lavage, and mucosal necrosis, inflammation, and fibrinopurulent exudate in airways. Observed changes were concentration related and appeared more pronounced in major airways near the point of entry (trachea in MB animals and nose in NB animals). One group of MB animals exposed for 10 min to 1454 ppm was evaluated at 3 and 14 wk after exposure; the acute effects had resolved by those times. The effects of 2-min exposures were consistently more severe than those from 10-min exposures to the same product of concentration x time. Exposures of MB animals for 60 min to 20 or 48 ppm HF did not result in observable adverse effects, although quasistatic pressure-volume curves were shifted upward slightly after 48 ppm. These data provide an integrated picture of the concentration-related effects of short nonlethal exposures to HF.

Administration, Inhalation↗
PubMed1998

Helminth levels of working donkeys kept under different management systems in the Moretele 1 district of the North-West Province, South Africa.

In Southern Africa, where 150,000 working donkeys provide an important alternative to mechanisation in resource-poor communities, very little is known about their helminth status, or about the impact of helminths on their work output. The aim of this study was to investigate the helminth status of working donkeys under different management systems. Donkey owners in three different areas (one rural and two semi-rural) of the Moretele 1 district of North-West Province, South Africa, were visited and structured interviews were used to assess the management systems under which the donkeys were kept. Faecal samples were collected from 93 donkeys in the study once a month for 14 months. Faecal samples were analysed for nematode and trematode eggs and cultured to produce third-stage larvae for the identification of the nematode species. Final comparisons between management system subgroups, as well as between areas, age groups and sexes were made. Four management systems were identified. (1) The first system identified consisted of donkeys which were kept in a small yard at all times. They were fed hay but no supplementary food. (2) The second system consisted of donkeys which were allowed to roam freely around the village most of the time and rounded up and held in an enclosure when needed for work. (3) The third system was identical to the second management system except that the donkeys were given supplementary food during winter. (4) The fourth system was only found in the one area where each owner owned 10 ha of land and here the donkeys were allowed to roam freely on the owner's land and brought into enclosures prior to working. Helminth species composition and faecal egg count numbers differed between these four systems. The main difference noted was that donkeys from management system one showed significantly higher numbers of strongyle eggs and higher percentages of some of the strongyle larvae. Management system two had a higher Strongyloides mean egg count and prevalence than the other areas. Parascaris and Gastrodiscus egg counts differed between all four systems. Since the results showed differences in the number and species of helminths in donkeys kept under the four management systems, suggestions are made as to which management system would facilitate reduction of helminth parasites in the animals. Although supplementary feeding in Moretele 1 is fairly rare, it would seem that donkeys which do have access to better food resources have lower egg counts than donkeys on limited grazing.

Age Distribution↗
PubMed1998

Expression patterns of the human papillomavirus type 16 transcription factor E2 in low- and high-grade cervical intraepithelial neoplasia.

Specific antibodies against the C-terminus of E2, produced by affinity purification of polyclonal antisera, have been used to identify the cellular populations which express the HPV 16 E2 transcription factor, in a series of formalin-fixed, paraffin-embedded cervical tissues. Cases were selected for both the presence of HPV 16 DNA (confirmed by multiple gene-specific PCR detections) and the presence of multiple grades of cervical intraepithelial neoplasia (CIN). The data indicate that E2 expression is highest in CIN I and in koilocytic lesions. Lower expression was observed in CIN II and little in CIN III lesions. In contrast, there was some restoration of E2 expression in invasive carcinomas, although the intracellular distribution was much more diffuse. The location of E2 expression to the superficial layers of the cervical epithelium, as well as the occurrence of some basal expression in CIN I, suggests that antibodies against HPV 16 E2 could be a useful adjunct to standard histological techniques for the detection of 'at-risk' patients as part of a cervical screening programme.

DNA-Binding Proteins↗
PubMed1998

Direct sequencing of the p53 gene shows absence of mutations in endometrioid endometrial adenocarcinomas expressing p53 protein.

AIMS: To investigate the mutational status of the p53 gene (Tp53) in endometrial carcinomas expressing p53 protein by direct gene sequencing. METHODS AND RESULTS: Eighteen cases of endometrial carcinoma, selected on the basis of p53 protein expression as detected immunohistochemically by the monoclonal antibody DO7, were microdissected in the p53 positive areas. DNA was extracted and subjected to polymerase chain reaction (PCR) for exons 5-8 which code for conserved areas containing mutational hot-spots. The PCR amplified material was then sequenced using an ABI automated sequencer and analysed using BLAST software at the NCBI web site. All sequences analysed were wild-type. CONCLUSION: The results confirm that expression of p53 protein may occur in endometrial adenocarcinoma without mutation and may be due to stabilization of the protein during its normal function, possibly by an mdm2 mediated process.

Adenocarcinoma↗
PubMed1998

Recent advances in the histopathology and molecular pathology of carcinoma of the endometrium.

Endometrial carcinoma is the commonest malignancy of the female genital tract. The pathogenesis is complex and at least three pathogenetic subtypes exist with different prognostic implications. The molecular events involved remain poorly defined but several genes are involved and mutations of tp53, WAF1/CIP1, PTEN, bcl-2 and c-erbB-2 have been implicated. Although care is needed in interpreting the results, the majority of these mutations can be detected immunohistochemically and therefore have the potential to aid the pathologist and surgeon in assessing the prognosis of a tumour. However, for the time being, no molecular marker is as valuable in determining prognosis as conventional parameters such as tumour type, grade and vascular space involvement.

Adenocarcinoma↗
PubMed1998

The hidden experience of radiotherapy to the head and neck: a qualitative study of patients after completion of treatment.

Only a small proportion of cancer patients undergo radical radiotherapy to the head and neck, but their needs are particularly complex. Radiation reactions often exacerbate existing functional difficulties and may severely limit 'normal' life. Few existing studies examine what happens when radiotherapy is over, yet this is the time when reactions are at their peak and day to day links with the hospital are severed. This naturalistic inquiry uses a combination of methods to explore the experiences of 12 patients after completion of radiotherapy to the head and neck. The impact of radiotherapy and the profound disruption to daily life is shown by the uncertainty and unpredictability of symptoms, the waiting, ambiguity and loss of self integrity which occurs throughout this time. Despite considerable physical and emotional trauma, patients showed remarkable resilience and a profound reluctance to ask for help. The findings demand that we re-examine our styles of communication, and consider how well we give information and listen to what is really happening. It is imperative that we provide greater consistency and continuity of care during radiotherapy, recognize the impact of the whole experience and respond to the post-treatment needs of this unique patient group.

Convalescence↗
PubMed1998

Aetiology, pathogenesis, and pathology of cervical neoplasia.

Early epidemiological studies of cervical neoplasia suggested a causal relation with sexual activity and human papillomaviruses (HPVs) have emerged as prime suspects as venerally transmitted carcinogens. HPVs fall into two broad camps: low risk types, associated with cervical condylomas and CIN 1; and high risk types (mostly 16 and 18), found in 50-80% of CIN 2 and CIN 3 lesions, and 90% of cancers. This association with cancer is very strong, with odds ratios of > 15 (often much higher) in case-control studies that are methodologically sound. An infrequently detected third group of intermediate risk type HPVs is associated with all grades of CIN and occasionally with cancers. HPVs have also been detected in a wide range of asymptomatic controls, indicating that other events are required for development of neoplasia such as viral persistence and/or altered expression of viral genes, often following integration of the viral genome. This leaves the two major viral oncogenes, E6 and E7, directly coupled to viral enhancers and promoters, allowing their continued expression after integration. High risk HPV E7 proteins bind and inactivate the Rb protein, whereas E6 proteins bind p53 and direct its rapid degradation. A range of putative cofactors has been implicated in progression: HLA type, immunosuppression, sex steroid hormones, and smoking; most of these cofactors appear to influence progression to CIN 3. The natural history includes progression to CIN 3 in 10% of CIN 1 and 20% of CIN 2 cases, whereas at least 12% of CIN 3 cases progress to invasive carcinoma. Cervical glandular intraepithelial neoplasia (CGIN) often coexists with squamous CIN, and the premalignant potential of high grade CGIN is not in doubt, but the natural history of low grade CGIN remains uncertain. A high proportion of CGIN lesions and adenocarcinomas are HPV positive, and HPV18 has been implicated more in glandular than in squamous lesions. A strong clinical case for the application of HPV typing of cells recovered from cervical scrapes can be made; however, a rigorous cost-benefit analysis of introducing HPV typing into the cervical screening programme is required. Prophylactic and therapeutic HPV vaccines are under development. This article reviews the aetiology, pathogenesis, and pathology of cervical neoplasia, emphasising the role of HPVs.

Carcinoma, Squamous Cell↗
PubMed1997

Immunohistochemical expression of inhibin/activin subunits in epithelial and granulosa cell tumours of the ovary.

Dimeric inhibin-A has been shown recently by a sensitive two-site ELISA assay to be a useful tumour marker in granulosa cell tumours of the ovary. It is also elevated in some patients with malignant epithelial ovarian tumours. To identify the precise subunits of inhibin expressed in ovarian tumours, three monoclonal antibodies, R1, E4, and INPRO (against the alpha C-, beta A-, and pro-alpha-subunits, respectively), were evaluated by immunohistochemistry on a panel of six granulosa cell and nine epithelial tumours. All granulosa cell tumours stained positively with E4 and R1, suggesting expression of dimeric inhibin-A; in two patients where serum levels were measured pre-operatively, they were elevated. The tumours also reacted weakly with INPRO, suggesting the presence of precursor forms of the alpha-subunit. Eight malignant epithelial ovarian tumours expressed the beta A-subunit only, as recognized by E4, while one tumour expressed both alpha- and beta A-subunits, which correlated with an elevated serum inhibin-A level. Thus, while granulosa cell tumours express inhibin, the majority of epithelial tumours probably express activin, a result which needs to be confirmed by serum measurements.

Activins↗
PubMed1997

Quality of life and patient preference for sequential versus continuous combined HRT: the UK Kliofem multicenter study experience. UK Continuous Combined HRT Study Investigators.

Hormone replacement therapy (HRT) must be taken for many years to attain the long-term benefits on osteoporosis and cardiovascular disease. However, this level of compliance with HRT is rarely achieved. This analysis documents the effect of continuous combined HRT with Kliogest on the relief of menopausal symptoms, and the patient preference for HRT over a 9-month treatment period. A total of 2151 postmenopausal women, of whom 1435 were currently on sequential therapy and 716 had not been previously treated, were enrolled from 55 centers in the UK. Women received a daily tablet of Kliogest for 9 months. Quality of life was assessed using the Greene Climacteric Scale, and the women completed patient preference questionnaires. Treatment with continuous combined therapy was at least as effective as previous sequential regimens in alleviating menopausal symptoms. By the study conclusion, patient preference was strongly in favor of Kliogest with 91% of completers preferring it to their previous sequential therapy. Improved quality of life and patient preference for continuous combined therapy may encourage long-term compliance with treatment, allowing more women to experience the long-term beneficial effects of HRT on osteoporosis and cardiovascular disease.

Aged↗
PubMed1997

Perception of airway obstruction in asthma: sequential daily analyses of symptoms, peak expiratory flow rate, and mood.

BACKGROUND AND OBJECTIVE: Studies have demonstrated a weak correlation between the degree of airways obstruction and the severity of asthma symptoms. Although the causes for this disparity are probably multiple, mood has been hypothesized to modulate symptoms. This investigation was designed to evaluate the effect of mood and other patient characteristics on the perception of airways obstruction. METHODS: We compared mood variables, symptom severity, albuterol use, and peak expiratory flow rate (PEFR) measured three times daily over a 21-day period in 21 adults with moderate to severe asthma. Electronic equipment was used for data collection. Analyses included both individual patient assessments and a within-subjects, time series, pooled regression of concurrent and time-lag data. RESULTS: After pooling 1323 observations, there was a weak concurrent relationship between symptoms and PEFR (beta = -0.17, p < 0.001). Only five patients (24%) were accurate perceivers, defined by a statistically significant relationship between symptoms and PEFR across time. Higher forced expiratory flow at 25% to 75% of capacity predicted perception accuracy (p = 0.004); active mood was marginally associated with accuracy (p = 0.06). These two variables together explained 41% of the variation in perception accuracy (p = 0.004). Mood did not independently predict symptoms, but conversely, increased symptoms predicted less pleasant mood (beta = 0.08, p < 0.001), less active mood (beta = -0.11, p < 0.001), and less active-pleasant mood (beta = 0.06, p < 0.001). PEFR did not predict mood, and only pleasant mood independently predicted higher PEFR (beta = 0.04, p < 0.05). Symptoms, but not PEFR, were concurrently associated with albuterol use (beta = 0.24, p < 0.001). CONCLUSION: The relationship between changes in PEFR and symptoms over time was generally poor. Those patients with lower FEF25-75 values tended to be less accurate perceivers. Mood states were influenced by asthma symptoms, but the converse was not true.

Adolescent↗
PubMed1997

Endometrial status in post-menopausal women on long-term continuous combined hormone replacement therapy (Kliofem). A comparative study of endometrial biopsy, outpatient hysteroscopy and transvaginal ultrasound.

Forty post-menopause women using a preparation of 2 mg 17 beta-oestradiol and 1 mg norethisterone acetate (Kliofem) for a mean duration of 2.9 years were investigated in an open, prospective, method comparison study. Main outcome measures were the histology of endometrial biopsy in comparison with clinical evaluation of the endometrium during panoramic hysteroscopy and endometrial thickness measured by transvaginal ultrasound. Thirty-six women had either an inactive atrophic or unassessable endometrial biopsy, the remaining four (10%) showed benign endometrial changes. In the majority of patients the endometrium had a thin and regular appearance on hysteroscopy (92.5% of cases) with an endometrial thickness not exceeding 7 mm (90% of cases). Non-agreement between histology and hysteroscopy or transvaginal ultrasound findings was associated with the presence of polyps and submucosal fibroids, or innocuous endometrial changes such as a pseudodecidual pattern. No case of malignancy was encountered in any patient in this study. The present study suggests that continuous combined hormone replacement therapy appears to be safe with regard to endometrial health. In the majority of women an inactive endometrium or non-assessable biopsy result will be encountered. However, the numbers examined here are small and endometrial carcinoma has been reported to occur. Continuing follow-up of patients on continuous combined HRT is therefore essential.

Adult↗
PubMed1997

cDNA cloning and pattern of expression of an adult, female-specific chymotrypsin from Aedes aegypti midgut.

A cDNA for a midgut chymotrypsin, induced by a blood meal, has been cloned and sequenced from the mosquito Aedes aegypti. The 938 base sequence codes for a 268 amino acid protein, which contains an 18-residue signal peptide and a seven-residue activation peptide. The deduced amino acid sequence contains several features typical of chymotrypsin proteases, including the catalytic triad of serine proteases and the residues that determine the chymotrypsin substrate specificity pocket. The chymotrypsin mRNA, absent in larvae, pupae, males and newly emerged females, reaches detectable levels within 24 h post-emergence and attains a maximum level 3-7 days after emergence. Translation of the chymotrypsin mRNA is induced by feeding a protein meal, and there is a dramatic increase in midgut chymotrypsin enzymatic activity after feeding. Chymotrypsin activity remained high during protein digestion, but chymotrypsin protein levels and enzymatic activity were almost undetectable once digestion was completed, 48 h after feeding.

Aedes↗