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S B Wharton

Publications and source records attributed to S B Wharton.

At least 37 records · Page 2Linked to original sources
PubMed2000

The significance of intratumoural neurones and neuronal differentiation in diffuse gliomas: a case series.

We describe four patients, ranging from 26-40 years of age, who presented with seizures and large, poorly circumscribed cerebral tumours on magnetic resonance imaging. The resected tumours demonstrated a histopathology similar to low-grade glioma, but with admixed mature neurones. Immunohistochemistry demonstrated expression of putative neuronal antigens in the neuronal component as well as in tumour cells which did not show neuronal morphology. These tumours did not have the usual radiological and pathological features typical of gangliogliomas, but demonstrated an infiltrative pattern of growth and subsequent progressive behaviour. The term ganglioglioma, with its implication of good prognosis, is therefore inappropriate for tumours of this type. The expression of "neuronal" antigens by astrocytomas requires further investigation.

Adult↗
PubMed2000

Expression of poly(ADP-ribose) polymerase and distribution of poly(ADP-ribosyl)ation in glioblastoma and in a glioma multicellular tumour spheroid model.

Development of necrosis is a characteristic feature of glioblastoma but its pathogenesis remains poorly understood. The process of poly(ADP-ribosyl)ation in response to DNA damage is mediated by poly(ADP-ribose) polymerase (PARP) and results in NAD+ depletion. The consequent ATP and energy depletion may result in cell necrosis. Therefore PARP activation is a potential candidate for a regulatory role in the pathogenesis of necrosis in glioblastoma. This study investigated whether there might be a relationship between both PARP expression and poly(ADP-ribosyl)ation, and necrosis in glioblastoma. The pattern of expression of PARP and of poly(ADP-ribose) groups in an archival series of glioblastoma was examined using immunohistochemistry. These parameters were also studied in multicellular tumour spheroids, derived from human glioma cell lines in which central necrosis develops with increasing spheroid diameter. Poly(ADP-ribose) groups were expressed in peri-necrotic tumour cells in glioblastoma. In the spheroid model poly(ADP-ribosyl)ation was seen centrally in pre-necrotic and necrotic cells with increasing spheroid diameter. PARP was widely expressed in viable tumour cells in the glioblastoma sections. In the spheroids, PARP expression, which was initially diffuse, became confined to the outer proliferative zone with increasing diameter. The pattern of expression of poly(ADP-ribose) groups in the spheroids and in glioblastoma raises the possibility that poly(ADP-ribosyl)ation may play a role in the development of necrosis in glioma. The high basal PARP expression in both glioblastoma and the spheroids suggests that this enzyme may have additional roles in glioma cell biology.

Adult↗
PubMed2000

Glomus jugulare tumour with metastases to cervical lymph nodes.

Glomus jugulare tumours are classically described as benign tumours with a long time course often measured in decades. Although these tumours may be locally invasive, most cases are histologically benign and metastases are rare. The case of a malignant glomus jugulare tumour with a particularly aggressive pattern of spread is presented. At the time of surgery, which was within 12 months of the development of symptoms, intracranial spread and metastasis to cervical lymph nodes had already occurred, demonstrating that glomus jugulare tumours are not always benign.

Adult↗
PubMed2000

Metastases from glomus jugulare tumours.

This review describes the features of glomus jugulare tumours with metastases. There were 100 sites of metastasis in the 53 cases previously reported. The sites of metastasis may be summarized as bone (33), lungs (23), lymph nodes (19), liver (nine) and other (16). Metastases presented up to 30 years after the initial treatment. The mean age of patients was 45 years and the sex ratio was approximately two females to one male, with no significant difference compared to non-metastatic tumours. There was a significantly higher incidence of pain and a significantly lower incidence of hearing loss at presentation compared to non-metastatic tumours. The commonest treatment was a combination of surgery and radiotherapy. The duration of symptoms before diagnosis was significantly shorter and the rates of persistent or recurrent local disease and death were significantly higher than for non-metastatic tumours. This review highlights the fact that glomus jugulare tumours are not always benign.

Glomus Jugulare Tumor↗
PubMed1999

Corneal epithelial toxic effects and inflammatory response to perfluorocarbon liquid.

We report an unusual case of corneal epithelial toxic effects associated with perfluorocarbon liquids (PFCLs). The clinical and histopathologic findings are described. An elderly man underwent vitreoretinal surgery for a complicated retinal detachment. Perfluorodecalin was used to repair the retina. It was left in situ for 8 weeks and removed via the pars plana. One month after removal of heavy liquids the patient developed a nonhealing corneal epithelial defect associated with limbitis. Perfluorodecalin was found under the superior conjunctiva. A conjunctival biopsy revealed the presence of vacuoles in the conjunctival stroma surrounded by an inflammatory response that consisted of lymphocytes, macrophages, and giant cells. On surgical removal of the PFCL from the subconjunctival space, the epithelial defect healed. The histopathologic and clinical evidence suggest that the inflammatory response and corneal epithelial ulceration were caused by the prolonged presence of PFCL in the subconjunctival space. To the best of our knowledge, PFCLs have not previously been reported to cause corneal epithelial defects or incite an inflammatory response in the human eye.

Aged↗
PubMed1999

Angiotropic large B-cell lymphoma with clinical features resembling subacute combined degeneration of the cord.

Angiotropic large cell lymphoma is a rare neoplastic disorder associated with a high mortality. The hallmark of the disease is lymphoid proliferation confined to the intravascular compartment without local tissue or vessel wall infiltration [1]. This feature is so striking that the disease was originally thought to arise from endothelial tissue and early cases were described as malignant angioendotheliomatosis. However, application of immunohistochemical methods for detection of lymphoid markers such as the CD45 and CD20 cell surface markers has confirmed its lymphoid origin, usually of B-cell lineage [2]. Clinical manifestations of the disease are protean and are due to multifocal medium and small vessel occlusion by tumour cells [3]. Characteristic sites of involvement are skin and central nervous system and although an ante-mortem diagnosis can be made from a biopsy specimen, it is often unsuspected [4]. We present a case of angiotropic large B-cell lymphoma in a 74-year-old man who presented with urinary symptoms and had a neurological picture resembling subacute combined degeneration of the cord.

Aged↗
PubMed1999

Intraocular metastases of cutaneous malignant melanoma: a case report and review of the literature.

Cutaneous malignant melanoma metastatic to the eye is rare but has been documented. The usual presentation is after the diagnosis of disseminated metastases. A 40-year-old Caucasian man presented with floaters and hazy vision due to ocular metastasis. He developed painful intractable rubeotic glaucoma leading to enucleation. Histopathological examination confirmed anterior segment tumour adherent to the iris that was consistent histopathologically with the primary cutaneous melanoma.

Adult↗
PubMed1999

Expression of Bcl-2 and Bax in oligodendrogliomas and their relationship to apoptosis.

Apoptotic bodies are frequently found in oligodendrogliomas, particularly in the anaplastic subtype. A range of proteins, such as those of the Bcl family, are implicated in the control of apoptosis. The ratio of antagonists of apoptosis, such as Bcl-2, to agonists, such as Bax, is thought to determine the outcome for a particular cell. This study aimed to determine the expression of Bcl-2 and Bax proteins in a series of oligodendrogliomas and to relate the expression of these to measures of apoptosis. Immunohistochemistry was used to detect the expression of Bcl-2 and Bax in an archival series of 32 oligodendrogliomas. The results were scored semiquantitatively for the extent and intensity of tumour staining. Apoptosis indices were determined by counting apoptotic bodies on haematoxylin and eosin staining and the percentage of cells showing a positive reaction with the TdT-mediated dUTP-biotin nick end-labelling technique (TUNEL). Granular cytoplasmic staining for Bcl-2 was seen in tumour cells in 81% of cases. Cases with a strong intensity (but not extent) of staining showed a lower TUNEL index (P=0.038). Bcl-2 expression was identified in the walls of intratumoural blood vessels in 55% of cases and in peri-tumoural neurones (where present) in 87%. Bax expression was detected in tumour cells in 69% of cases but no relationship to TI was detected. Bax positivity was seen in blood vessels in 44% of cases and peri-tumoural neurones in 60%. Bcl-2 and Bax were concluded to be expressed in a high proportion of oligodendrogliomas, suggesting that they may exert a regulatory role in cell death in these tumours.

Apoptosis↗
PubMed1999

Systemic metastases of glioblastoma multiforme.

The case history of a 40-year-old man who developed systemic metastases 2 years after treatment for glioblastoma is reported. The diagnosis was confirmed by biopsy. The role of immunohistochemistry in the diagnosis of this rare event is discussed and illustrated.

Adult↗
PubMed1999

Effects of N-6 essential fatty acids on glioma invasion and growth: experimental studies with glioma spheroids in collagen gels.

OBJECT: Intracranial infusions of gamma-linolenic acid (GLA), an essential fatty acid, have been used as an adjuvant therapy following malignant glioma resection; however, little is known about the dose response of glioma cells to this therapy. In this in vitro study the authors address this important pharmacological question. METHODS: Glioma spheroids derived from U87, U373, MOG-G-CCM, and C6 cell lines were grown in collagen gel and exposed to a range of GLA concentrations (0-1 mM) for 5 days. The diameter of glioma spheroids was measured, the apoptotic index was assessed using both the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling technique and cell morphological testing, and the levels of proliferating cell nuclear antigen were also measured. CONCLUSIONS: The dose-response patterns were similar for all four glioma spheroids. Low concentrations of GLA (<100 microM) increased both apoptosis and proliferation with a net increase in tumor growth and invasion, whereas high-dose GLA (>100 microM) significantly impaired spheroid cell growth. The proliferative effects of low-dose GLA could be a hazard in the clinical treatment of malignant glioma; however, because of the low toxicity of GLA against normal cells, local delivery of millimolar doses of GLA could significantly reduce tumor size.

Animals↗
PubMed1998

Expression of neuronal markers in oligodendrogliomas: an immunohistochemical study.

The oligodendroglioma has been considered to be a tumour showing oligodendrocyte differentiation, but studies of the expression of oligodendrocyte markers have not conclusively demonstrated this and the pattern of differentiation of this tumour remains uncertain. Recent studies have suggested that some oligodendrogliomas may show neuronal differentiation. The aim of this study was to determine whether there was evidence of neuronal differentiation in a series of oligodendrogliomas, and, if so, to determine whether this identified a biologically or clinically distinct group. Immunohistochemistry was carried out on paraffin sections using antibodies to synaptophysin, phosphorylated and non-phosphorylated neurofilament proteins. An archival series of 32 oligodendrogliomas had been previously characterized for histological features, histological grade, Ki-67 labelling index, apoptosis index and prognosis. Six per cent of tumours showed expression of synaptophysin. Thirty-one per cent of cases showed expression of neurofilament proteins with an antibody to non-phosphorylated epitopes, but no cases were positive with antibodies to phosphorylated neurofilament epitopes. Tumours showing expression of neuronal markers did not show a difference in the distribution of histological grade or GFAP expression from those which did not express these markers, and there was no difference in labelling indices or prognosis between the two groups. In conclusion, a subset of oligodendrogliomas showed expression of neuronal lineage markers; this is discussed in relation to histogenesis and differential diagnosis. The expression of such markers did not identify a biologically or clinically distinct subgroup.

Biomarkers↗
PubMed1998

Apoptosis in human primary brain tumours.

Apoptosis, or programmed cell death, has been recognized for nearly three decades as occurring in many organs in response to different pathophysiological stimuli. It is now recognized as one of the fundamental cellular biological processes. In human glioma it was initially identified as 'shrinkage necrosis'. This review outlines the characteristics of apoptosis in the various types of primary human brain tumours. The significance of apoptosis is reviewed in relation to normal and tumour cell dynamics, cellular susceptibility to normal and oncogenic signals and to potential therapeutic advances. On a practical level, methods which are currently used to analyse different aspects of the apoptotic process are introduced. These techniques for analysing apoptosis are critically evaluated and compared. Current developments elucidating the diverse pathways of apoptosis signalling are also reviewed. The potential of pro-apoptotic therapy for the treatment of gliomas is discussed.

Apoptosis↗
PubMed1998

Proliferation and cell death in oligodendrogliomas.

The rates of cell proliferation and of cell loss influence the growth rate of a tumour and reflect genetic changes. We studied proliferation and apoptosis in oligodendrogliomas and their relationship to progression of the tumours. Thirty-two cases of oligodendroglioma were retrieved spanning a 10-year period. The diagnosis and grade were reviewed and follow-up data obtained. Mitotic index (MI) and apoptotic index (AI) were determined from haematoxylin and eosin (H & E) stained sections. A labelling index (LI) of proliferating cells was obtained using the MIB1 antibody to the Ki-67 antigen. A further index of apoptosis was obtained using in situ end-labelling of DNA strand breaks (TUNEL index, TI). Fourteen cases were graded as II, 18 as III (1993 WHO). LI was significantly higher in grade III than in grade II tumours (P < 0.01) but the difference in apoptotic indices between grades was not significant. There was a significant (P = 0.036) positive correlation between the logarithms of TI and LI. Construction of survival curves demonstrated a significant difference in survival according to histological grade (P < 0.05). Stratification of cases by LI alone did not predict significantly different survival outcomes, and apoptotic indices did not demonstrate a relationship to survival. A positive relationship was demonstrated between proliferation and apoptosis in oligodendrogliomas. The levels of apoptosis observed indicate that this phenomenon may have an important influence on the overall rate of tumour growth.

Adolescent↗
PubMed1997

Chondrosarcoma of the petrous apex. Dilemmas in diagnosis and treatment.

A case of chrondrosarcoma of the petrous temporal bone is presented. Chondrosarcomas rarely occur intracranially and typically present apex mass. The dilemmas faced in the diagnosis and treatment of petrous apex chondrosarcomas are discussed. This case also gives interesting insight into the natural history of this tumour.

Chondrosarcoma↗
PubMed1996

Paravertebral muscles in disease of the cervical spine.

OBJECTIVES: Cervical spine disorders are common in the older population. The paravertebral muscles are essential to the support and stabilisation of the cervical spine but have been little studied. The aim was to determine whether pathological changes develop in these muscles in patients with severe cervical spine disease, which, if present, might contribute to the pathogenesis and symptomatology of their disorder. METHODS: Open biopsies of superficial and deep paravertebral muscles were obtained during the course of surgical procedures to alleviate cervical myelopathy. Most of these patients had cervical spondylosis or rheumatoid arthritis involving the cervical spine. The biopsies were compared with muscle obtained at necropsy from patients without a history of cervical spine or neuromuscular disorder. RESULTS: Muscle from both the study and control groups showed a similar range and severity of abnormalities. In several patients, grouped fibre atrophy suggested chronic partial denervation. Most biopsies showed type 1 fibre predominance and selective type 2 fibre atrophy. Ragged red fibres were a frequent finding and electron microscopy disclosed accumulations of mitochondria, a small proportion of which contained rounded, or longitudinally oriented, single osmiophilic inclusions. Fibres containing core-like areas were also frequent. These pathological features were seen with increasing severity and frequency with increasing age. CONCLUSIONS: The paravertebral cervical muscles develop pathological abnormalities with increasing age with both neurogenic and myopathic features, the pathogenesis of which is probably multifactorial. Such a muscle disorder would be expected to be accompanied by functional impairment which may contribute to the development and symptomatology of cervical spine disease with increasing age.

Aged↗