Biomedical subjects
Publications and source records attributed to P R Millard.
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.
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.
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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.
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.
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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.
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.
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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.
This study aimed to investigate the effects of the faecal stream and stasis on the mucosa of ileal pouches. Nine patients were followed up. Two pouch biopsy specimens were obtained from each at the time of pouch formation, ileostomy closure, and three, six, and 12 months after operation. None developed pouchitis. Two pouch biopsy specimens each were also obtained from 20 patients (six with pouchitis), whose pouches had been functioning for at least a year and in whom pouch evacuation was assessed by radioisotope labelled artificial stool. Biopsy specimens were assessed for the degree of acute and chronic inflammation, mucin type (high iron diamine-alcian blue stain), a morphometric index of villous atrophy (villous height:total mucosal thickness), and crypt cell proliferation (using the monoclonal antibody Ki67). Mean values from the two biopsy specimens were obtained for each parameter. After three months of pouch function, the scores for acute and chronic inflammation, the degree of sulphomucin, and crypt cell proliferation were significantly higher, and the index of villous atrophy was significantly lower (indicating a greater degree of villous atrophy), than at pouch formation or at ileostomy closure. The values at pouch formation and ileostomy closure were similar. For all parameters, the changes seen at six and 12 months were not significantly different from those at three months. There was no significant correlation between the efficiency of pouch evacuation and any of the mucosal changes. It is concluded that exposure to the faecal stream is necessary for changes to take place in the pouch mucosa, although the amount of stasis, as measured by radioisotopic evacuation studies, seems to be irrelevant. The mucosal changes occur soon after ileostomy closure and then remain stable for at least one year.
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Whole antiserum, IgG, and a greater than 99% pure F(ab')2 preparation were compared for their ability to enhance Lewis renal allografts in DA recipients. Despite having unimpaired antigen-binding capacity, the DA anti-Lewis F(ab')2 was virtually ineffective at the highest dose tested, and was calculated to be a minimum of 100 times less effective than whole antibody. The administration of a 10-fold excess of F(ab')2 before an effective dose of IgG did not block the enhancing effect of the latter.
Cyclophosphamide was tested for its interaction with passive enhancement in suppressing the rejection of kidney allografts in the (DA x Lewis)F1 to Lewis rat strain. Dose response studies with cyclophosphamide showed that 10 mg/kg/day for 14 days was necessary for complete suppression of rejection and indefinite graft survival. Doses of 5 and 3.5 mg/kg/day had only a marginal effect on graft function and survival, although the lymphocytotoxin response to the graft was completely or very substantially suppressed by these smaller doses. The use of passive enhancement with cyclophosphamide at the 5- and 3.5-mg/kg/day doses resulted in a favourable interaction with improved graft function and survival. Interestingly, passive enhancement in combination with 5 mg/kg/day of cyclophosphamide resulted in indefinite graft survival only if cyclophosphamide was given for 28 days. If cyclophosphamide was given for 14 days, rejection was suppressed only during the period of cyclophosphamide treatment.
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Cyclophosphamide and antilymphocyte serum (ALS) were compared for their ability to suppress renal allograft rejection in the rat. These two agents were chosen since they are generally considered to act on different arms of the immune response, and might therefore complement each other's action. Dose response studies showed that both agents could suppress rejection completely. There were no differences in their ability to suppress the lymphocytotoxic antibody response to the graft and the histological patterns of rejection were similar. There was no evidence that cyclo-phosphamide was more effective in suppressing vascular lesions. The doses of both agents which suppressed the lymphocytotoxic antibody response were substantially lower than those required to suppress graft rejection. When suboptimal doses of the two agents were administered together, the combinations were found to be additive and not synergistic.