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Biomedical subjects

P R Millard

Publications and source records attributed to P R Millard.

At least 19 recordsLinked to original sources
PubMed1999

Paget's disease of the vulva associated with local adenocarcinoma and previous breast adenocarcinoma: report of two cases.

We report two women in whom vulval Paget's disease occurred in association with local adenocarcinoma and previous breast adenocarcinoma. The first patient presented at the age of 83 years with moist erythematous changes over the perineum and an indurated area near the anus. Biopsy of the indurated area showed Paget's cells throughout the epidermis and, below, adenocarcinoma infiltrating the dermis. Ten years previously, she had undergone a left mastectomy for infiltrating ductal carcinoma of the breast. The second patient was diagnosed as having Paget's disease at the age of 74 years. A vulval biopsy showed Paget's cells in the epidermis but, in addition, there were changes suggestive of adenocarcinoma of the sweat glands. Her symptoms of vulval itching had started at the age of 45 years and had led to a simple vulvectomy at the age of 57 years. Retrospective review of this vulvectomy specimen showed Paget's disease. She had also previously been treated for infiltrating ductal adenocarcinoma of the breast and adenocarcinoma of the rectum. The management of Paget's disease is difficult because of its high recurrence rate and, as illustrated by our two cases, treatment is difficult if the patients are elderly and in poor general health.

Adenocarcinoma↗
PubMed1999

An infective aetiology for vulval lichen sclerosus re-addressed.

Although there is evidence to support an autoimmune basis for lichen sclerosus, there have also been some studies which suggest an infective aetiology. These include reports of the presence of spirochaetal forms with Steiner silver stains and purplish coccoid forms with Fite stains. We have repeated these studies on vulval biopsies obtained from 16 patients with vulval lichen sclerosus. Using the Steiner silver method we found no evidence of spirochaetal forms in any of the specimens. With the Fite stain we observed purple-staining coccoid forms within the dermis of 13 of the 16 lichen sclerosus specimens. However, these coccoid forms also stained strongly positive with toluidine blue, suggesting they were mast cell granules rather than micro-organisms. We were therefore unable to demonstrate evidence for an infective aetiology in vulval lichen sclerosus, although this cannot yet be excluded. Further work is also needed to understand the significance of mast cells in lichen sclerosus.

Adult↗
PubMed1995

The localization of the target antigens and antibodies in linear IgA disease is heterogeneous, and dependent on the methods used.

Fifty-nine patients with linear IgA disease, 24 with onset in childhood and 35 with adult onset, were studied. Sera from all patients were tested by indirect immunofluorescence, using as substrates intact normal skin and normal skin which had been split through the lamina lucida region of the basement membrane zone by suction and by prolonged incubation with molar NaCl. This enabled the site of the target antigen for the circulating IgA antibodies to be determined. The sites of deposition of the IgA antibodies in vivo were detected by raising a suction blister in eight patients, and splitting seven patients' biopsies by prolonged incubation with molar NaCl. Eighteen sera were positive with intact skin, and 34 with split skin. Twenty-nine sera were positive with suction blisters as substrate; 14 bound to the epidermal aspect of the split skin, seven in a combined pattern (binding to the epidermis and dermis) and six to the dermal aspect. Thirty-one sera bound to salt-split skin, 24 to the epidermal side and seven on the dermal side. There was discordance between the two methods of skin splitting in 15 sera. Seven sera gave a combined pattern with suction but with salt-split skin, five of these bound epidermally, one was dermal, and one negative. Five sera showed epidermal binding on salt-split skin and were negative on suction blisters, and the reverse was seen with one serum. Two sera gave variable results on suction blisters. Direct immunofluorescence studies showed dermal binding on all eight patients with suction blisters, and epidermal binding in four and dermal binding in three patients with salt splitting.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Sensory and sympathetic ganglia in HIV-1 infection: immunocytochemical demonstration of HIV-1 viral antigens, increased MHC class II antigen expression and mild reactive inflammation.

Sensory and sympathetic ganglia from 12 cases of human immunodeficiency virus type 1 (HIV-1) infection, all but one without clinical evidence of peripheral nerve disease, were studied immunocytochemically for their content of lymphocytes, macrophages, MHC Class II antigens and HIV-1 and cytomegalovirus antigens. They were compared with ganglia from 7 normal and peripheral nerve disease control cases. Compared with normal controls, many of the ganglia from the majority of HIV-1-infected subjects contained more T lymphocytes and macrophages and enhanced MHC class II expression. A few also showed occasional neuronal degeneration which was not present in the normal controls. In 7 cases HIV-1 gp41 envelope protein and/or p24 core protein antigens were detected in intraganglionic macrophages. Sensory ganglia contained more gp41 HIV-1 antigen than sympathetic ganglia. There was no clear correlation between detection of HIV-1 antigens in ganglia and in the CNS. Detection of HIV-1 antigens in ganglia was more common in cases of HIV-1 infection that had progressed to clinical AIDS by the time of death (71%) than in those that had not done so (40%). It is concluded that there is commonly a mild ganglionitis which is asymptomatic in the absence of detailed clinical testing and frequently associated with local presence of HIV-1 antigens in sensory and sympathetic ganglia in AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1993

A clinicopathological study of scarring alopecia.

We have studied 10 cases of scarring alopecia, and investigated the diagnostic reliability of immunofluorescence and histopathology in lichen planopilaris and pseudopelade. In the light of our findings, we discuss the possible pathomechanisms of both disease processes.

Adult↗
PubMed1993

Suction-induced basal cell cytolysis in the Weber-Cockayne variant of epidermolysis bullosa simplex.

In the Weber-Cockayne form of epidermolysis bullosa simplex (EBS-WC), trauma induces blisters which are confined to the palms and soles. Histologically, basal cell cytolysis is seen. We studied 6 patients with EBS-WC to determine the ultrastructural level at which artificially-induced suction blisters form. Blisters were raised by application of a suction blister cup to uninvolved forearm skin, the cup being connected to a negative pressure of 200 mm of mercury. The blisters were biopsied and examined by light and electron microscopy. On light microscopy, all biopsies showed marked vacuolization of keratinocytes in the lower two-thirds of the epidermis, and in all but one there was a cleavage plane through the basal keratinocytes. These findings were confirmed by electron microscopy in 4 patients. The separation through the basal cells is in contrast to the situation in normal individuals in whom cleavage occurs below the level of the basal cells, within the lamina lucida. Thus, even apparently normal skin from non-acral sites has the same structural abnormality as the affected acral sites in EBS-WC.

Adolescent↗
PubMed1992

A search for Pneumocystis carinii in post-mortem lungs by DNA amplification.

DNA amplification of specific sequences and subsequent oligonucleotide hybridization were used to search for Pneumocystis carinii in post-mortem lung samplings from non-immunosuppressed individuals ranging from 15 to 70 years of age. No P. carinii-specific DNA was detected in 45 DNA amplification reactions from 15 lungs.

Adolescent↗
PubMed1992

The effect of immediately preoperative adjuvant radiotherapy in the surgical treatment of primary cutaneous malignant melanoma.

A historical series of patients with primary cutaneous malignant melanoma is reviewed. These patients had been treated with a single therapeutic dose of irradiation to the tumour and surrounding skin immediately before surgical excision. Some patients had also received a single necrotising dose of radiotherapy to the tumour itself. Recurrence and survival rates have been examined retrospectively in the light of reviewed histology, and compared with other published series. Preoperative radiotherapy was found to have no significant influence on the outcome of surgical treatment of primary malignant melanoma.

Adolescent↗
PubMed1992

Variation in the deposition of the antibodies at different anatomical sites in linear IgA disease of adults and chronic bullous disease of childhood.

The diagnosis of linear IgA disease of adults (LAD) and chronic bullous disease of childhood (CBDC) relies upon finding a linear band of IgA at the basement membrane zone on direct immunofluorescence. This study examines the regional variation in antigen expression in the skin of affected individuals. Direct immunofluorescence was performed on biopsies from four different sites in 17 patients with these diseases. In two patients a biopsy from the volar surface of the forearm was negative, but other sites were positive; in the remaining patients there was no variation in antibody expression with site. It is therefore recommended that, if a single diagnostic biopsy is to be taken, the volar surface of the forearm is avoided.

Adolescent↗
PubMed1992

Nasal mucosal involvement in lupus erythematosus.

The involvement of oral, conjunctival and genital mucosa in lupus erythematosus (LE) has recently been described. Reports of nasal involvement have been sporadic. A prospective study was performed to assess the prevalence of nasal symptoms and signs in LE and to identify the incidence of deposition of immunoreactants in the nasal mucosa of patients with LE. Thirty-six patients with LE were studied; 21 had non-specific nasal symptoms and 12 had evidence of chronic inflammatory changes in the mucosa of the nasal cavity or in the vestibule (septal perforation, inflamed mucosa, vestibulitis). Immunoreactants were found in only 4 patients and did not correlate well with clinical evidence of disease. Nasal mucosal involvement in LE is underestimated and often overlooked in the assessment of such patients.

Adult↗
PubMed1991

Fate of oligodendrocytes in HIV-1 infection.

The brains of 22 HIV-1-infected cases and 11 controls, matched for age and sex, were studied with immunocytochemical reactions specific for oligodendrocytes, astrocytes, microglia and HIV-1. In HIV-1 infection, mild degrees of myelin damage were associated with an increase in oligodendrocyte numbers, a change that was reversed in the presence of severe damage. Severity of myelin damage correlated with the extent of astrocytic and microglial reactions expressed in a semi-quantitative manner. HIV-1 p24 antigen was detected in all cases with severe myelin damage and a smaller proportion of cases with lesser degrees of myelin damage. It is concluded that, in HIV-1 infection, oligodendrocytes undergo an initial reactive hyperplasia which may represent an attempt to repair myelin damage.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed1991

Hailey-Hailey disease: a widespread abnormality of cell adhesion.

Suction has been used to investigate cell adhesion in clinically normal skin in Hailey-Hailey disease. We have demonstrated that there is a widespread subclinical abnormality in keratinocyte adhesion in this disease. There may be a synthesis of functionally deficient adhesion junctions, increased breakdown of adhesion junctions or abnormalities in other adhesion proteins in the epidermis in Hailey-Hailey disease. The findings contrast with those in Darier's disease in which abnormal cell adhesion was only demonstrable in clinically involved skin.

Adult↗
PubMed1991

The treatment of vulval lichen sclerosus with a very potent topical steroid (clobetasol propionate 0.05%) cream.

The clinical and histological response to 12 weeks of treatment with a very potent topical fluorinated steroid was studied in 15 patients with vulval lichen sclerosus (LS) who were treated with twice daily applications of clobetasol propionate 0.05% cream (Dermovate, Glaxo U.K.). Thirteen patients completed the study and all showed a marked clinical improvement. Histological measurements of skin biopsies taken before and after treatment showed a significant reduction in the characteristic features of LS. One patient developed contact sensitivity to clobetasol propionate. There was no evidence of infection or skin atrophy during the study. Patients completing the study have been followed up for up to 22 months and have been maintained in remission with moderately potent topical steroids which had previously been ineffective.

Administration, Topical↗
PubMed1991

The predictive value of histological classification into degrees of differentiation of squamous cell carcinoma of the larynx and hypopharynx compared with the survival of patients.

In the course of running two clinical trials between 1966 and 1985, data became available for 1315 patients, 713 in the first trial and 602 patients in the second trial, which has allowed comparison between histological findings in laryngeal and hypopharyngeal carcinoma, the observed survival and the tumour-free rates for these patients who were followed for up to 10 years. Extensive histopathology reviews have revealed over 98% agreement on tumour cell type between the initial report and that of the reviewer. Highly significant differences have been found for squamous cell carcinoma between the observed survival and the tumour-free rates for patients with well-differentiated and with anaplastic lesions. There was a statistically significant greater proportion of patients with well-differentiated tumours at larynx sites and in stage 1 when compared with patients with anaplastic tumours, but even when this was taken into account, multivariate analyses showed that tumour grading still made an independent significant contribution to the prediction of prognosis. For squamous cell carcinoma only very simple and rapidly assessed histopathological features need to be identified to classify tumours into the two grades employed in this study. The analyses have confirmed the prognostic significance of tumour grading in squamous cell carcinoma in the larynx and hypopharynx.

Carcinoma, Squamous Cell↗
PubMed1991

Mucosal characteristics of pelvic ileal pouches.

This study aimed to investigate the degree of colonic metaplasia in ileo - anal pouches. Biopsy specimens from 25 patients with functioning pouches, eight of whom had pouchitis, were studied using routine histology, mucosal morphometry, mucin histochemistry, and immunoperoxidase staining with monoclonal antibodies directed towards a 40kD colonic protein and a small bowel specific disaccharidase-sucrase isomaltase. Thirteen patients (including all eight with pouchitis) had subtotal or total villous atrophy and crypt hyperplasia. In this group, nine had colorectal type sulphomucin and the 40kD colonic protein was detected in two. These changes were not observed in patients with less severe villous abnormalities. Sucrase-isomaltase activity was, however, present in all 25 pouch specimens. We conclude that although some ileal pouches acquire certain colonic characteristics, complete colonic metaplasia does not occur.

Adenomatous Polyposis Coli↗