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I A Cree

Publications and source records attributed to I A Cree.

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

Rhinostomies: an open and shut case?

AIMS: To analyse bone fragments from rhinostomies of patients undergoing revisional dacryocystorhinostomy, looking for evidence of new bone formation. METHODS: 14 consecutive patients undergoing secondary lacrimal surgery were included in this study. In each case the existing rhinostomy was enlarged with bone punches, care being taken to use the punches with the jaws cutting perpendicularly to the edge of the rhinostomy, to allow accurate orientation of the specimens. The fragments were examined histologically for evidence of new bone formation. RESULTS: Histological sections showed fragments of bone with variable fibrosis at the edge of the rhinostomy. There was evidence of only very little new bone formation. CONCLUSION: This study has clearly shown that, at the edge of a rhinostomy, healing is predominantly by fibrosis and there is only very limited new bone formation.

Aged↗
PubMed1999

Ring melanoma--a rare cause of refractory glaucoma.

BACKGROUND: Ring melanoma of the ciliary body and iris is extremely rare and often has adverse histology. This tumour may cause raised intraocular pressure. METHODS: A review of four cases of ring melanomas with insidious presentations seen in the ocular oncology service over a 12 month period. RESULTS: All four patients presented with unilateral anterior segment abnormalities and refractory glaucoma. The misdiagnoses of the causes of the glaucoma included angle recession from previous blunt trauma (patient 1); iridocorneal endothelial (ICE) syndrome supported by endothelial specular microscopy (patients 2 and 3); and melanocytoma on ciliary body biopsy (patient 4). Two patients were treated by several cyclodiode ciliary body ablation treatments and the other two underwent trabeculectomies and Molteno tubes. Two of the four patients have since died from their disease. CONCLUSION: The ophthalmologist should re-evaluate the diagnosis in patients with anterior segment abnormalities and refractory ipsilateral glaucoma. Endothelial specular microscopy and biopsy of the suspicious lesion may give misleading reassurance. The potential presence of an anterior uveal melanoma must always be considered.

Adult↗
PubMed1999

Modelling uveal melanoma.

BACKGROUND/AIM: There has been no consistent pattern reported on how mortality for uveal melanoma varies with age. This information can be useful to model the complexity of the disease. The authors have examined ocular cancer trends, as an indirect measure for uveal melanoma mortality, to see how rates vary with age and to compare the results with their other studies on predicting metastatic disease. METHODS: Age specific mortality was examined for England and Wales, the USA, and Canada. A log-log model was fitted to the data. The slopes of the log-log plots were used as measure of disease complexity and compared with the results of previous work on predicting metastatic disease. RESULTS: The log-log model provided a good fit for the US and Canadian data, but the observed rates deviated for England and Wales among people over the age of 65 years. The log-log model for mortality data suggests that the underlying process depends upon four rate limiting steps, while a similar model for the incidence data suggests between three and four rate limiting steps. Further analysis of previous data on predicting metastatic disease on the basis of tumour size and blood vessel density would indicate a single rate limiting step between developing the primary tumour and developing metastatic disease. CONCLUSIONS: There is significant underreporting or underdiagnosis of ocular melanoma for England and Wales in those over the age of 65 years. In those under the age of 65, a model is presented for ocular melanoma oncogenesis requiring three rate limiting steps to develop the primary tumour and a fourth rate limiting step to develop metastatic disease. The three steps in the generation of the primary tumour involve two key processes-namely, growth and angiogenesis within the primary tumour. The step from development of the primary to development of metastatic disease is likely to involve a single rate limiting process.

Adult↗
PubMed1998

Multifocal choroiditis: clinicopathologic correlation.

Many of the white dot syndromes are considered to have a granulomatous pathogenesis. The histopathologic characteristics of this case of multifocal choroiditis seen within 15 months of apparent clinical onset show that the white dot lesions were nongranulomatous perivascular choroidal infiltrates, consisting mainly of B lymphocytes. Early choroidal neovascularization was also seen.

Adult↗
PubMed1998

Limbal vernal keratoconjunctivitis in the tropics.

OBJECTIVE: This study aimed to describe the pathology of vernal keratoconjunctivitis (VKC) in children from Kenya. DESIGN: Case series. PARTICIPANTS: Ten patients with clinically active and untreated limbal VKC and five age-matched control subjects without external eye disease were recruited from a district eye hospital in Kenya. MAIN OUTCOME MEASURES: Paraffin sections of limbal and tarsal conjunctiva were examined by tinctorial and immunocytochemical methods to characterize the inflammatory infiltrate. RESULTS: In comparison with control subjects, patients with VKC were more likely to show squamous metaplasia of the tarsal conjunctiva. The patients with VKC had cellular infiltration of both the stroma and epithelium consistent with chronic inflammation, particularly in the biopsy specimens taken from the limbus. In tarsal conjunctiva, the stromal infiltrate consisted of a diffuse T-lymphocyte reaction with clustering of B-lymphocytes; mast cells, immunoglobulin E (IgE) plasma cells, and eosinophils also were prominent. Mast cells and eosinophils were found within the epithelium in the more severely inflamed biopsy specimens. CONCLUSIONS: These features are similar to those in reports of VKC in temperate regions, although the degree of B-lymphocyte clustering is greater in tropical patients with VKC. Although none of the patients had other symptoms of atopy, the authors findings are consistent with those for an allergic basis for this disease.

Adolescent↗
PubMed1998

Use of an ex vivo ATP luminescence assay to direct chemotherapy for recurrent ovarian cancer.

Chemotherapy for recurrent ovarian carcinoma (ROC) produces response rates of 10-80% depending on the prevalence of platinum resistance. Most patients relapse within 1 year and median progression-free survival (PFS) is generally no more than 6 months. Previous pretherapeutic chemosensitivity assays mostly failed to improve the outcome of patients with ROC. Newly developed ATP assays show promising retrospective correlation with clinical outcome. We report here the first results of ATP assay-directed chemotherapy in patients with ROC. Therapy was selected by the ATP tumor chemosensitivity assay (ATP-TCA) in a prospective open-label pilot trial for ROC. Objective response rate (ORR), PFS and overall survival (OAS) of the first 25 evaluable patients were retrospectively compared with those of 30 others having similar characteristics who were treated empirically within the same period. The actuarial median observation times were 80 weeks for the ATP-TCA group and 83.5 weeks for the control group, respectively. In the control group, a 37% ORR [two complete responses (CR) and nine partial responses (PR)] was followed by a median PFS of 20 weeks and a median OAS of 69 weeks, mainly related to the use of single-agent chemotherapy. The ORR in the ATP-TCA group was 64% (eight CR and eight PR) (p=0.04) with the majority of responses (11 of 16) achieved with novel combinations. The median PFS in this group was 50 weeks (p=0.003) and the median OAS was 97 weeks (p=0.145). Survival of responding patients was similar in both groups. Chemotherapy guided by the ATP-TCA produced a greater benefit with regard to both ORR and PFS in platinum-refractory patients. ATP-TCA-directed chemotherapy for ROC compares favorably with chemotherapy chosen by a clinician and often leads to the choice of novel drug combinations. These promising results now warrant confirmation by prospective randomized trials.

Adult↗
PubMed1998

The prognostic significance of c-myc oncogene expression in uveal melanoma.

The role of the c-myc oncogene has been little investigated in uveal melanoma. In this study an analysis of c-myc oncoprotein expression was undertaken using flow cytometry in 71 patients with posterior uveal melanoma. Nuclear c-myc oncoprotein was detected in all of the tumours, and survival analysis revealed a significant association between high oncoprotein positivity and improved survival (log rank test: chi2 = 6.47, P = 0.01). Multifactorial analysis using Cox's proportional hazards model revealed nuclear c-myc oncoprotein to be an independent prognostic marker more accurate than other clinicopathological parameters (log rank test: chi2 = 6.61, P = 0.01). However, this result of high oncoprotein expression correlating with improved outcome is surprising and in contrast to our previous studies using the same method on cutaneous melanoma, where high levels of nuclear c-myc expression have been found to correlate with poor outcome both in primary and secondary disease. This study suggests that the pattern of oncogene expression in uveal melanoma is distinct from cutaneous melanoma and that the underlying biology of these tumours is different.

Adolescent↗
PubMed1998

New model of conjunctival scarring in the mouse eye.

AIMS: To establish a simple model of conjunctival wound healing in the mouse eye. METHODS: 4 week old BABL/c mouse eyes were studied over a 14 day period. Surgical procedure under general anaesthesia involved a blunt dissection of the conjunctiva performed by injection of 25 microliters of PBS via a 27 gauge needle into one eye, while the contralateral eye was used as control. Mice were assessed clinically and sacrificed at 1, 2, 3, 7, and 14 days after surgery. Enucleated eyes were prepared for histological analysis. Development of scar tissue was studied with haematoxylin and eosin, oxidation aldehyde fuchsin, and van Gieson stains, with assessment of cellularity, extracellular matrix formation, and wound characterisation. RESULTS: Histological analysis revealed a marked and characteristic healing response initiated by a predominantly granulocytic inflammatory reaction at day 1 with peak fibroblast activity 3 days after surgery. Oxytalan fibres and newly laid collagen fibres were detected early in the subconjunctival wound area and up to 7 days after surgery. Remodelling and complete organisation of scar tissue was evident by day 14. CONCLUSION: A single subconjunctival injection in the mouse eye results in a marked and consistent healing response. This represents a simple, inexpensive, and reliable animal model of conjunctival scarring. The mouse is a biologically well characterised animal model and allows the use of a wide variety of molecular tools. There are potentially significant clinical applications, in particular in investigating the effects of modulating agents such as antimetabolites, growth factors, and their antagonists on conjunctival scarring.

Animals↗
PubMed1998

Leprosy transmission and mucosal immunity: towards eradication?

The declining prevalence of leprosy has not been matched by a declining incidence. Widespread adoption of multiple drug therapy (MDT) in closely monitored control programmes has not prevented transmission of Mycobacterium leprae. Despite the rarity of lepromatous patients, most of those living in endemic areas have immunological evidence of exposure to M. leprae. This paradox could be explained if, for many such individuals, infection was transient, did not result in disease development, but did allow the transmission of infection to other individuals. There is increasing evidence from nasal PCR studies that such sub-clinical transmission may exist and that mucosal immune responses to M. leprae may develop during resolution of initial infection. Sub-clinical infection appears to occur in clusters and may require close contact over a prolonged period for optimal transmission. Control of transmission may be feasible through identification and treatment of individuals within infection clusters, allowing progress towards the eradication of leprosy.

Humans↗
PubMed1997

Infiltrating inflammatory cell phenotypes and apoptosis in rejected human corneal allografts.

PURPOSE: The aim of this study was to survey the histopathological and immunohistochemical features of rejected human corneal allografts. METHODS: Following graft failure in each case due to rejection, paraffin-embedded specimens of 17 corneal transplants which had been replaced were examined by light microscopy and immunohistochemistry. Specimens were either first (n = 9), second (n = 4) or third (n = 4) grafts and were removed at varying intervals from 4 weeks following documented rejection. RESULTS: Those grafts which were removed earliest following onset of rejection had the most intense graft inflammatory infiltrates. Immunohistochemical staining showed a high proportion of graft stroma-infiltrating cells expressing leucocyte common antigen, and many of these cells also bore T cell or macrophage markers. Leucocyte-keratocyte apposition and regional loss of keratocytes were observed in all rejection specimens, but not in non-rejected control grafts. In situ end-labelling of DNA double-strand breaks and morphological features identified keratocyte apoptosis in 5 of 12 specimens examined for this phenomenon. Corneal endothelial cells were absent in 7 specimens and present in reduced numbers in the remaining 10 specimens. CONCLUSIONS: Endothelial cell monolayer attenuation and keratocyte loss are consistent findings in grafts removed subsequent to clinically observed endothelial rejection. Death of donor corneal cells is mediated, at least in part, by apoptosis. The stromal inflammatory infiltrate consists mainly of T lymphocytes and macrophages, which may be responsible for induction of keratocyte apoptosis.

Adult↗
PubMed1997

Individualizing chemotherapy for solid tumors--is there any alternative?

The burgeoning understanding of the molecular basis of carcinogenesis and tumor drug resistance is matched by an appreciation of the complexity of individual tumors. This complexity underlies the heterogeneity of response to treatment and is a major barrier to improving the outcome of solid tumor chemotherapy. While individualization of chemotherapy is theoretically attractive, past attempts to provide such information have produced many papers and little progress. However, the disparate molecular make-up of tumors of the same clinicopathologic type suggests that there may be no alternative and recent progress suggests that individualization of cancer therapy could have considerable benefits. In this review, we consider the alternative methods which might be employed and the requirements which need to be met before they are introduced. It will be some time before molecular analysis can predict chemosensitivity, although this may prove feasible for more specific agents than those currently in use. However, newly developed cellular chemosensitivity assays such as the ATP-tumor chemosensitivity assay allied to selected molecular measurement may already have the potential to select optimal therapy for patients. We need to develop a diverse series of acceptable and biologically logical regimens for each of the common tumor types, all of which can be tested in vitro.

Antineoplastic Agents↗
PubMed1997

The ex vivo chemosensitivity profile of choroidal melanoma.

Uveal melanoma has a high mortality rate and responds poorly to existing chemotherapy. We have therefore examined the sensitivity of uveal melanoma to cytotoxic agents using an ex vivo chemosensitivity assay to determine whether some agents which have not been used for this tumor might have activity. An ATP-based tumor chemosensitivity assay (ATP-TCA) was used to determine the effect of nine cytotoxic drugs at multiple dilutions in 28 primary uveal melanoma specimens. Evaluable assay results from up to 16 tumors with each drug showed variable sensitivity to alkylating agents (three of nine with mitomycin C, one of 15 with cisplatin and seven of 15 with treosulfan), cytosine arabinoside (seven of 16), paclitaxel (one of five) and doxorubicin (two of 16). No tumors were sensitive to temozolomide, or 5-fluorouracil, and only one of 14 to vincristine. The combination of treosulfan with cytosine arabinoside resulted in enhanced tumor cell inhibition in three of five tumors tested. Combinations containing paclitaxel combined with doxorubicin or cisplatin showed some activity, but none achieved 100% inhibition and the results were similar to those obtained with paclitaxel alone. Uveal melanoma shows considerable heterogeneity of sensitivity to cytotoxic drugs, with considerable resistance to most agents, matching clinical experience. The results suggest that cytosine arabinoside or gemcitabine plus treosulfan may be an active combination. Clinical trials will commence shortly. The use of the ATP-TCA provides a method of testing multiple agents and combinations in a way which would be otherwise impossible in rare tumors such as uveal melanoma.

Antineoplastic Agents↗
PubMed1997

Reassessment of the PAS patterns in uveal melanoma.

BACKGROUND: Previous work has highlighted the prognostic importance of patterns of periodic acid Schiff (PAS) staining (the Folberg patterns) in uveal melanoma. These patterns have been ascribed to blood vessels but the patterns are different from those seen with other staining techniques for blood vessels. It has recently been shown that microvessel density is the dominant prognostic factor in uveal melanoma. This study reinvestigates the nature and significance of the PAS patterns. METHODS: The PAS patterns were compared with the patterns seen with conventional connective tissue stains and with the patterns seen in sections stained for the presence of blood vessels (by immunohistochemistry for factor VIII related antigen). The PAS patterns were determined on a panel of 117 cases of uveal melanoma. The prognostic significance of each of these patterns was determined and, as more than one pattern can exist in a tumour, principal components analysis was performed to determine the number of underlying factors. RESULTS: Comparison of the PAS patterns with other stains demonstrates that they are based on connective tissue including fibrovascular tissue. Five of the nine PAS patterns carried prognostic significance on univariate analysis. Principal components analysis suggested that these patterns represented three underlying factors, which were tentatively identified as representing disordered growth (factor 1), emergence of rapidly growing subclones (factor 2), and section orientation (factor 3). CONCLUSIONS: The PAS patterns are based on fibrovascular tissue and can be ascribed to three underlying factors. The first two of these factors carried prognostic significance and the first (disordered growth) retained independent prognostic significance in a multivariate Cox model which included microvessel density and tumour size.

Biomarkers, Tumor↗