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Biomedical subjects

M Leader

Publications and source records attributed to M Leader.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1996

Chondroblastoma--an unusual site in a young patient.

We report a case of primary chondroblastoma presenting as a submucosal lump on the nasal bridge of a 15-year-old female. The lesion was curetted and the patient remains well after one year follow-up. This case report describes a primary chondroblastoma arising in an unusual site and in an unusual age group.

Adolescent↗
PubMed1996

Porphyrin metabolism in hepatitis C infection.

Hepatitis C virus has been implicated as a major precipitating factor in porphyria cutanea tarda (PCT). To determine whether hepatitis C infection alone is sufficient to induce PCT, we screened two groups of patients with hepatitis C infection. The first group comprised women who had become HCV positive secondary to immunization with anti-D immunoglobulin (group 1). Group 2 included males and females who were HCV positive but HIV negative secondary to intravenous drug abuse. Though both groups had very abnormal liver function tests, we found no significant abnormalities in porphyrin metabolism in these groups of patients. Therefore, in this study population, we conclude that HCV infection alone is insufficient to cause porphyrin metabolic derangement.

Adolescent↗
PubMed1996

Proliferation indexes--a comparison between cutaneous basal and squamous cell carcinomas.

AIMS: To compare differences in cell proliferation indexes and apoptotic indexes between cutaneous basal and squamous cell carcinomas, in an attempt to suggest an explanation for the differences in their biological behaviour. METHODS: Forty cases of cutaneous basal cell carcinoma (BCC) and 40 cases of moderately and well differentiated squamous cell carcinoma (SCC) were retrieved from the archives. Sections, 4 microns thick, were cut from formalin fixed, paraffin wax embedded tissue in each case and stained with haematoxylin and eosin. These were then examined for mitotic and apoptotic figures per 1000 cells. Sections from the same cases were also immunostained with the mouse monoclonal antibody Ki67 (MIB1); positive nuclear staining was counted per 1000 cells. RESULTS: No significant differences were found between the mitotic indexes and apoptotic indexes in these tumours. There was, however, a significant difference in Ki67 (MIB1) staining, with greater staining in the squamous cell carcinomas. CONCLUSION: Estimation of the mitotic and apoptotic indexes did not reveal any differences between these two tumour types. The proliferation indexes, assessed by Ki67 immunostaining, did differ. This may be one of the factors underlying the more aggressive behaviour of SCC.

Apoptosis↗
PubMed1996

DNA ploidy, expression of p53 protein and metastatic behaviour of gastric carcinoma.

DNA ploidy of 57 gastric carcinomas with metastases (12 liver, 1 adrenal, 4 ovary and 48 lymph node) were measured by flow cytometry. DNA anueploidy was significantly related to liver metastases: 9 out of 12 gastric carcinomas with liver metastases were anueploid (75%) as compared to 13 out of 45 (28.8%) of cases without liver metastases (P < 0.01); the one gastric carcinoma with adrenal metastasis was also anueploid. DNA ploidy was not related to ovarian or lymph node metastases. Another interesting finding was that all of 3 gastric carcinomas with liver metastases which showed a diploid DNA pattern, expressed p53 protein, while all of 3 carcinomas with liver metastases but no p53 protein expression were anueploid. The expression of p53 protein was not related to ovarian metastases. The results suggested that an anueploid DNA pattern and the expression of p53 protein are both objective markers valuable in predicting high risk potential of metastases to the liver, and that the combined detection of these markers can be a most useful method in the follow-up of patients with gastric carcinoma in detecting those at high risk of developing metastases following surgical resection. Also the poorer prognosis of patients with gastric carcinoma showing an anueploid DNA pattern may be related to the development of distant organ metastases through the blood vascular system. Furthermore, the clone of gastric carcinoma cells which accumulate p53 protein or show an anueploid DNA pattern may have a causative role in the development of liver (& adrenal) metastases.

Adenocarcinoma↗
PubMed1995

DNA ploidy status in 84 ocular melanomas: a study of DNA quantitation in ocular melanomas by flow cytometry and automatic and interactive static image analysis.

Deoxyribonucleic acid (DNA) ploidy was quantified in 84 ocular melanomas (median follow-up, 11-years) by flow cytometry, CAS 200 interactive image analysis, and Pathology Image Processing Environment (PIPE; Department of Quantitative Pathology, Free University, Amsterdam, The Netherlands) automatic image analysis (75). Overall, 32.1% of the melanomas were aneuploid, 2.3% were tetraploid, and 66.6% were diploid. Pathology Image Processing Environment analysis estimated DNA ploidy in 12 tumors that were unprocessable by flow cytometry. Of 10 tumors that were diploid by flow cytometry, PIPE detected stemline aneuploidy in five and some aneuploid cells in five more. Seven tumors were aneuploid by PIPE but diploid by CAS 200, five of which contained occasional DNA aneuploid cells on the CAS 200 histograms. Pathology Image Processing Environment analysis quantified tumor samples with an average of 500 (250 to 1,050) cells in less than 10 minutes. All cells classified as spindle A according to the Callender system (more than 10,000) were diploid. Spindle B and epithelioid cells occupied both diploid and aneuploid peaks on the DNA histograms. Dioxyribonucleic acid variables did not correlate with established prognosticators, such as Callender cell type, largest tumor dimension, or glaucoma, nor did they reach significance by univariate and multivariate analyses. The value of these findings as a diagnostic support in uveal melanoma, particularly in combination with fine needle aspiration biopsy, is discussed.

DNA, Neoplasm↗