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Biomedical subjects

M Leader

Publications and source records attributed to M Leader.

At least 19 recordsLinked to original sources
PubMed2000

Swelling and delamination of multi-electrode sensor arrays studied by variable-pressure scanning electron microscopy.

Multi-electrode sensor arrays are made of soft and wet materials not easily examined by most microscopic techniques. In this paper, we have demonstrated that low-vacuum scanning electron microscopy (LVSEM) and energy-dispersive X-ray analysis (EDX) are adequate for studying the hydration, swelling, and possible delamination of multi-electrode sensor arrays. We found that the LVSEM environment had no detectable effect on the morphology of Na(+), K(+), and Ca(++) sensors, and EDX analysis indicated that all three membranes have similar compositions. However, once hydrated, the sensors exhibited different behaviors. The K(+) and Ca(++) sensors swelled more than the Na(+) sensor did. This swelling is due principally to water sorption in the membrane. We believe that the larger thickness of the K(+) and Ca(++) membrane is partly responsible for the observed swelling effect. A simple Griffith analysis of the interface rupture confirms the experimental evidence that these thicker membranes also are more prone to delamination failure.

Biocompatible Materials↗
PubMed2000

Deterioration of giant cell arteritis with corticosteroid therapy.

BACKGROUND: Failure of response of giant cell arteritis (GCA) to corticosteroid therapy has invariably been attributed to the delay in diagnosing the disease or the use of inadequate corticosteroid dosage. Following our observation of progressive deterioration following the introduction of prednisolone use in a patient, we examined the possibility that worsening of the condition might be due to corticosteroid therapy rather than coincidence. OBJECTIVE: To determine whether corticosteroid therapy may exacerbate GCA. DESLGN: Case report and an analysis of similar cases reported in the medical literature. PATIENT: A 64-year-old man had a 3-month history of headache, night sweats, malaise and general weakness, and anorexia and weight loss and a more recent history of jaw claudication, dysphagia, and hoarseness. Clinical findings included prominent temporal arteries with absent pulsation, abnormal saccades to the right, and eyelid retraction. Laboratory findings included an elevated erythrocyte sedimentation rate and platelet count. Results of a biopsy of the temporal artery confirmed GCA. Magnetic resonance imaging scans showed ischemic cerebellar lesions and a mature infarct in the left anterior occipital, posteroparietal region. Following corticosteroid therapy commencement, the patient's condition deteriorated steadily for 5 days with clinical signs suggestive of an evolving vertebrobasilar stroke. Following treatment with high-dose intravenous dexamethasone sodium phosphate and heparin sodium, his symptoms improved. DATA SOURCES: The review included analysis of autopsy-based reports in which clinical details are provided and clinical reports in which major visual or cerebral complications are described. Significant complications occurred in many cases shortly following the introduction of corticosteroid therapy. In many of these cases, the symptoms indicated that GCA had been present for a significant period prior to corticosteroid therapy. CONCLUSIONS: Progressively evolving occlusive strokes may occur following corticosteroid therapy in patients with GCA. In cerebrovascular complications, vascular occlusion occurs at sites of active vasculitis, usually within the vertebrobasilar system. It is not certain that the worsening of the condition following corticosteroid therapy is always coincidental, and an alternative possibility, namely a functional relationship between the initiation of corticosteroid therapy and clinical deterioration, should be borne in mind.

Adrenal Cortex Hormones↗
PubMed2000

Expression of CD44 in uterine cervical squamous neoplasia: a predictor of microinvasion?

OBJECTIVE: CD44, an integral membrane glycoprotein, may have an important role in early tumorigenesis, specifically, facilitating early tumor progression. Reports of the expression of CD44 in early uterine cervical squamous carcinogenesis are conflicting. We examined the expression of CD44 in microinvasive carcinoma of the cervix (MIC), as yet unreported, and compared it to that in cervical intraepithelial neoplasia (CIN) 1 and CIN 3 to further elucidate its role in early squamous carcinogenesis. METHODS: Seventeen cases of CIN 1, 24 cases of CIN 3, and 20 cases of MIC were stained with antibodies to CD44s, CD44v5, and CD44v6. Only membranous staining was considered positive. RESULTS: Positive membranous staining (>50% cells) was observed in 97% of cases of CIN 1 using all three antibodies. In CIN 3, positive staining was seen more often with CD44v6 (18/24) and CD44v5 (19/24) than with CD44s (6/24). Expression of CD44v6 was retained more often in MIC (16/20) compared with CD44s (3/20) and CD44v5 (9/20). Those cases of CIN 3 and MIC that failed to meet our criteria for positive staining showed either heterogeneous or absent staining. CONCLUSION: There is a qualitative and quantitative reduction in expression of CD44 in MIC and CIN 3 compared with CIN 1. Down-regulation of CD44 variants may occur later in neoplastic progression than CD44s. This pattern may reflect their important biological function in early progression by cervical cancer cells. Patchy and heterogeneous staining in more advanced lesions limits the usefulness of CD44 and its variants in the assessment of microinvasion.

Adult↗
PubMed2000

A simple and rapid technique for the detection of Epstein-Barr virus DNA in HIV-associated oral hairy leukoplakia biopsies.

A method of generating nucleic acid probes by polymerase chain reaction (PCR) for the detection of Epstein-Barr virus (EBV)-DNA by in situ hybridization in oral hairy leukoplakia (OHL) lesions is described. This method has the advantage over older methods of being cheaper, quicker and retaining sensitivity and specificity. Purified PCR products of Epstein-Barr virus DNA of 110 bp and 328 bp were labelled with biotin by nick translation or random primer labelling and were compared in in situ hybridization experiments with probes prepared by incorporation of biotin-labelled nucleotides in the PCR reaction mixture, with EBV viral DNA as a template. These probes were applied to 18 OHL tongue biopsies known to be positive for EBV-DNA, using a commercially available biotin-labelled BamHI "V" fragment EBV-DNA probe. To determine the specificity of the probes, we applied them to 20 normal tongue tissue samples and to 12 biopsies taken from keratotic tongue lesions from patients without risk factors for HIV infection and known to be negative for EBV-DNA. Clear positive signals for EBV-DNA were detected in all 18 cases of OHL biopsies using the amplimer of 328 bp labelled by PCR and random primer labelling. However, nick translation labelling was less efficient and sensitive. All control specimens were negative for EBV-DNA.

AIDS-Related Opportunistic Infections↗
PubMed2000

Replication error phenotype, clinicopathological variables, and patient outcome in Dukes' B stage II (T3,N0,M0) colorectal cancer.

AIMS: To examine the relation between the replication error (RER) phenotype and other genetic events, clinical features, and long term survival in patients with Dukes' B stage II (T3,N0,M0) colorectal cancer. METHODS: RER phenotype was investigated in 159 patients by PCR amplification of microsatellite marker loci on chromosomes 5q, 17p, 17q, and 18q from tumour DNA extracted from archival tissue. Data on activating c-Ki-ras mutations were available from a previous study. Immunohistochemical detection of p53 and c-erbB-2 expression was performed on paraffin wax embedded tissue. RESULTS: Of 159 colorectal cancers studied, 22 (14%) were RER+ while 137 (86%) were RER- for two or more loci. RER+ tumours were more commonly located in the right colon, tended to be larger than RER- tumours, and were more often poorly differentiated than RER- cancers. No significant associations were seen between RER status and the presence of a mutant c-Ki-ras gene, or between RER status and p53, c-erbB-2, or c-myc gene expression. Univariate survival analysis showed that outcome was similar in RER+ and RER- cases. Multivariate survival analysis showed that the relative risk of death for patients with RER+ cancers was 0.95 that of patients with RER- cancers. CONCLUSIONS: The results suggest that, while the RER phenotype may be associated with some differences in tumour pathology (site, size, differentiation), it is not associated with the genetic alterations studied or with significant differences in long term survival.

Aged↗
PubMed1999

Malignant lymphoma of the cervix. An unusual presentation and a rare disease.

Malignant lymphomas arising in the uterus are uncommon and are more commonly seen in the cervix than the corpus. Involvement of the cervix as part of a systemic lymphoma is more common than primary lymphoma, but the cervix as the site of presentation is unusual. We report two cases of malignant lymphoma of the cervix. The first patient, a 52-year-old woman, was referred to colposcopy following persistent low grade dyskaryosis on cervical cytology. At colposcopy a Lletz biopsy was performed and a diagnosis of CIN 1 and focal CIN 2 was made. In addition the subepithelial zone revealed a non-Hodgkin's (NHL) B-cell follicular lymphoma. The patient was subsequently staged as NHL Stage 3E. The second patient, a 35-year-old woman, was referred to the gynaecology department with a history of abnormal vaginal bleeding and two abnormal smears. Subsequent cervical biopsy revealed a high grade, large cell, malignant lymphoma, diffuse, B-cell. The patient was staged as Stage IE. Primary lymphoma of the uterine cervix as illustrated in the second case is very unusual. One case had negative cytology and one case had abnormal cells of uncertain origin. This highlights the difficulty of diagnosing cervical lymphoma, a rare but treatable malignancy, on cytology and suggests that cervical biopsy is needed for the confirmation of the diagnosis.

Adult↗
PubMed1999

Multiple perifollicular fibromas.

Perifollicular fibroma is a benign mesodermal tumour of the hair follicle. It can occur as a solitary papule or as multiple lesions that are clinically indistinguishable from other tumours of the pilar apparatus. Multiple perifollicular fibromas may be inherited although the pattern remains unclear. Adnexal tumours can be associated with internal malignancy and perifollicular fibromas have been linked with adenomatous colonic polyps. This report describes a patient with multiple perifollicular fibromas with no associated malignancy to date and a family pedigree suggestive of an autosomal dominant pattern of inheritance.

Adult↗
PubMed1998

Diphenylhydantoin sodium promotes early and marked angiogenesis and results in increased collagen deposition and tensile strength in healing wounds.

BACKGROUND: Sodium diphenylhydantoin (DpH) (phenytoin) was first introduced as an antiepileptic in 1938. One of its side effects, gingival hyperplasia, prompted investigation into the possible application of this drug as a promoter of wound healing. Since the late 1950s phenytoin has been used in a variety of clinical situations. However, its exact mechanism of action is still debated. The aim of this study was to determine the effect of DpH on wound healing in an incisional rat model. METHODS: A four dorsal wound model was used, and each cephalad wound had a polyvinyl alcohol sponge placed in a subcutaneous pocket just above its cephalad end. Caudal and cephalad wounds were treated with 10 mg DpH in 200 microliters carrier, and the other two wounds received an equal volume of the saline vehicle as controls on the day of wounding and on the third and sixth postoperative days. The animals were killed on the tenth postwounding day. Tensile strength of fresh and fixed scars was determined using constant speed tensiometry, and wound hydroxyproline was determined spectophotometrically. RESULTS: There was a highly significant increase in both fresh and fixed wound tensile strength of all DpH-treated wounds compared with controls (p < 0.001). This was reflected by a significant increase in polyvinyl alcohol sponge hydroxyproline in DpH-treated wounds compared with saline-treated wounds (p = 0.002). Histologic examination of these wounds was performed at 3 and 6 days after wounding. There was moderate fibroblast infiltration with a marked inflammatory infiltrate and neovascularization in the DpH-treated wounds compared with controls at 3 days. By day 6, the inflammatory infiltrate had almost totally receded in the treated wounds, but fibroblast infiltration and angiogenesis were still persistently marked. In comparison, the saline-treated wounds still had moderate inflammatory and fibroblast infiltrate and mild angiogenesis. CONCLUSIONS: DpH alters the natural course of wound healing and may be of benefit in clinical situations where defective wound collagen deposition may lead to poor wound healing and consequent morbidity and mortality.

Animals↗
PubMed1998

Langerhans cells in benign, premalignant and malignant skin lesions of renal transplant recipients and the effect of retinoid therapy.

BACKGROUND AND DESIGN: Langerhans cells (LC) are a unique population of antigen-presenting cells in the epidermis which may play a role in the defense mechanisms against skin tumors. Renal transplant recipients (RTRs) have a significantly increased incidence of premalignant and malignant skin lesions. Langerhans cells, which are important for local immune surveillance, may be depleted or downregulated in skin neoplasms of RTRs, facilitating their growth. We investigated the Langerhans cell densities in 29 squamous cell carcinomas (SCCs), five basal cell carcinomas (BCCs), four Bowen's disease, eight dysplastic lesions (actinic keratoses), and three viral warts from 15 RTRs and compared these to the Langerhans cell densities in normal control skin. Eleven RTRs were receiving low-dose etretinate as chemoprophylaxis for recurrent skin cancer and the effect of low-dose retinoid therapy on Langerhans cell densities in SCCs from these patients was also assessed. Langerhans cells in frozen tissue sections were stained with the anti-human Leu-6 monoclonal antibody. RESULTS: There was no significant difference in LC numbers between normal skin from RTRs and normal skin from non-immunosuppressed individuals. There was a statistically significant reduction in LC/mm2 and LC/1000 K (keratinocytes) for SCC, BCC, dysplastic lesions and viral warts compared with normal skin (P < 0.001, P < 0.01, P < 0.001, P < 0.05, respectively). There was a trend for an increase in Langerhans cell density in SCCs which developed during etretinate therapy compared with pre-etretinate but the difference was not statistically significant. CONCLUSIONS: In this study of RTRs, a significant reduction in Langerhans cell densities was observed in SCCs, BCCs and dysplastic lesions compared with normal skin. A reduction in Langerhans cell density in viral warts from RTRs was also observed. A working hypothesis may include a multifactorial etiology for this reduction in Langerhans cell densities. It is possible that human papilloma virus (HPV) infection, by reducing intraepidermal Langerhans cell density, may decrease local immune surveillance and facilitate the development of skin cancers. Ultraviolet radiation and immune suppression may also play a role. The marked depletion of Langerhans cells in skin cancers, precursor lesions and viral warts suggests a central role for Langerhans cells in skin cancer promotion in RTRs.

Basal Cell Carcinoma↗
PubMed1997

p53 tumor suppressor gene protein expression in premalignant and malignant skin lesions of kidney transplant recipients.

BACKGROUND: Kidney transplant recipients have an increased incidence of skin cancer, the cause of which is likely multifactorial. Inactivation of the tumor suppressor gene p53 protein may be important. Chemoprophylaxis of skin cancer with retinoids is beneficial in these patients. OBJECTIVE: Our purpose was to investigate the immunohistochemical expression of p53 protein in premalignant and malignant cutaneous lesions in kidney transplant recipients and the effect of low-dose etretinate on p53 expression. METHODS: Paraffin sections were stained with the monoclonal antibody DO-7. RESULTS: Immunoreactivity of p53 was observed in 59% of basal cell carcinomas and more than 60% of squamous cell carcinomas, Bowen's disease, dysplastic lesions, and viral warts. No demonstrable effect of etretinate on p53 expression could be determined. CONCLUSION: The high prevalence of p53 immunoreactivity in premalignant and malignant skin lesions of kidney transplant recipients supports a role for p53 protein in skin cancer. This could be caused by mutation of the p53 gene, inactivation, or failure of degradation of p53 protein.

Adult↗
PubMed1997

The effect of light drinking on HCV liver disease: the jury is still out.

We carried out a study to determine if light drinking (1 unit alcohol/d) adversely affected liver histology in hepatitis C virus (HCV)-associated liver disease. Twenty-eight women who developed chronic hepatitis C (all genotype 1b) as a result of receiving contaminated anti-D immunoglobulin (Ig) had their alcohol intake assessed. Group I (n = 8) took no alcohol, Group II (n = 8) consumed less than one unit monthly and Group III (n = 12) took between two and 18 units (mean = 6.7 units) per week. All 28 subjects had a liver biopsy performed and their histology scored according to the global Knodell score (KI) and the international score for both inflammatory grading (II) and fibrotic staging (FI). The three scores were compared between the three groups and differences tested for significance. The median score for the three groups were Group I: KI = 2, II = 2 and FI = 0; Group II: KI = 4, II = 3.5 and FI = 0.5; Group III: KI = 5.5, II = 4 and FI = 1.5. Initial analysis showed that there was no difference between those who abstained from alcohol and those with a less than monthly consumption; these groups were united and compared with the light drinkers. On Mann-Whitney U test analysis, the P values for the differences between the light drinkers and the combined groups were 0.666 (KI), 0.159 (II) and 0.080 (FI) These results show a trend towards greater histological abnormality in people drinking one unit of alcohol per day, but larger groups will need to be assessed to determine if this is a true or chance finding.

Adult↗
PubMed1997

Determination of testicular function after torsion by DNA flow cytometry of serial fine-needle aspirates.

OBJECTIVE: To determine the efficacy of DNA flow cytometric analysis of testicular percutaneous fine-needle aspirates in the assessment and follow-up of testicular function after torsion, and to determine the relationship between the duration of torsion and testicular injury. MATERIALS AND METHODS: Three groups of 15 adult rats underwent a 720 degrees torsion, with fixation of the mesorchial ligament, for 1, 3 or 5 h. Bilateral aspirations, performed 7, 21 and 35 days after torsion were examined by flow cytometry. Testes were harvested and evaluated histologically using Johnsen's scoring. RESULTS: Irreversible testicular injury occurred in all three groups of rats, with loss of function after 1 h and loss of viability after 3 and 5 h. The results from flow cytometry suggested significant contralateral testicular injury (P < 0.025) but this was not supported by the histological evaluation. There was a strong correlation between the testicular function assessed by flow cytometry and by Johnsen's scoring of histological specimens (r2 = 0.95). CONCLUSION: The assessment of testicular aspirates by flow cytometry allows testicular function to be followed after torsion in rats, and potentially in humans. Using DNA flow cytometry, the temporal course of the twisted testis in the adult rat was determined; contralateral testicular injury following the reversal of torsion could not be excluded.

Animals↗
PubMed1997

Ploidy profile of morphologically normal squamous epithelium adjacent to high grade cervical intraepithelial neoplasia.

We have investigated the ploidy profile of morphologically normal mucosa adjacent to high grade CIN (n = 16) and also from normal cervix (n = 18). DNA ploidy was assessed using flow cytometry and image analysis. All cases were diploid by both modalities. Our results show that morphologically normal squamous mucosa has a stable ploidy profile even when it lies adjacent to high grade CIN. This finding supports the view that high grade CIN is a neoplastic expansion of transformed cells rather than the result of a field change effect.

Epithelium↗
PubMed1997

Screening of patients with iron overload to identify hemochromatosis and porphyria cutanea tarda.

OBJECTIVE: To assess the importance of iron overload as a risk factor for porphyria cutanea tarda (PCT). DESIGN: Prospective study during a 4-month period. SETTING: Departments of emergency care, gastroenterology, and dermatology in a tertiary referral center. PATIENTS: Patients were deemed eligible for inclusion in the study if serum ferritin levels were greater than 500 micrograms/L (normal range: females, < 125 micrograms/L; males, < 325 micrograms/L). MAIN OUTCOME MEASURES: Porphyrin excretion profiles were analyzed on all patients included in the study, where clinically relevant. A diagnosis of PCT was confirmed biochemically in all cases. The HLA typing was then performed on newly diagnosed cases of PCT. RESULTS: Of 4127 patients tested, 240 patients with an elevated serum ferritin level were identified, of whom 74 had an elevated serum ferritin level of more than 500 micrograms/L. Of the latter group, 17.5% had hemochromatosis and 6.7% had PCT. The incidence of PCT in the hemochromatosis group was 23%; HLA typing revealed the presence of at least 1 of the hemochromatosis markers. CONCLUSIONS: A high serum ferritin level in the absence of evident cause should prompt investigation for both hemochromatosis and PCT. The HLA heterozygosity for hemochromatosis in some patients with PCT may be a cause of hepatic siderosis.

Adult↗
PubMed1996

An image analysis study of DNA content in early colorectal cancer.

The DNA content of 168 consecutive T3,N0,M0 (Dukes' B, Astler-Coller B2) colorectal cancers was studied using image analysis on formalin-fixed paraffin-embedded tissues. 72 cases (43%) were classified as diploid and the remaining 96 (57%) as non-diploid. After a median follow-up period of 6.7 years, a significant survival advantage was found for diploid compared with non-diploid cases (logrank test; P = 0.008). The long-term (8 year) survival rate was 70% for diploid and 46% for non-diploid tumours. Subgroup analysis showed that the survival advantage conferred by tumour diploidy was greatest in large (> or = 5 cm) cancers and was found both in colonic and rectal cancer cases. These data indicate that tumour ploidy status measured by image analysis might be useful in determining risk of colorectal cancer recurrence and death in patients following resection of early colorectal cancer.

Adult↗