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Biomedical subjects

Marjorie Fowler

Publications and source records attributed to Marjorie Fowler.

11 recordsLinked to original sources

Treatment of refractory temporal arteritis with adalimumab.

High-dose corticosteroids (CS) are the mainstay of treatment for temporal (giant cell) arteritis (TA). A usually required long-term treatment with CS, ranging from 1 to 5 years or more, frequently leads to serious side effects in about 60% of patients. There is no conclusive evidence about the role of immunosuppressive agents like methotrexate and azathioprine in the treatment of TA. There are few reports of treatment of refractory or steroid-dependent TA with tumor necrosis factor alpha (TNF-alpha) inhibitors including infliximab and etanercept. TA is characterized by infiltration of the vessel wall by macrophages, giant cells, and T lymphocytes, with production of several cytokines responsible for the acute phase response. TNF-alpha has been demonstrated in up to 60% of the cells in all areas of inflamed arteries by immunohistochemical techniques; hence, it could play a pivotal role in the pathogenesis of TA. We report the first case of resistant TA, which was treated successfully with adalimumab, a fully human recombinant IgG1, anti-TNF-alpha monoclonal antibody. The efficacy of TNF-alpha inhibitors in resistant TA should be studied in larger, controlled studies.

Adalimumab↗

Central pontine myelinolysis, an update.

Central pontine myelinolysis (CPM) can be regarded as one of the demyelinating syndromes. First described by Adams et al. in 1959 in their chronic alcoholic patients, it has now been described in the malnourished, the chronically debilitated, the renal, the hepatic and the transplant patient among others. Pathologically, it is defined as a symmetric area of myelin disruption in the center of the basis pontis, although similar symmetric lesions have also been described occurring with CPM as well as independently in other brain areas (extrapontine myelinolysis or EPM) including the cerebellar and neocortical white/gray junctional areas, thalamus and striatum. Possible mechanisms include a hyperosmotically induced demyelination process resulting from rapid intracellular/ extracellular to intravascular water shifts producing relative glial dehydration and myelin degradation and/or oligodendroglial apoptosis. The process most often occurs during rapid rebalancing of the electrolyte parameters in the hyponatremic patient. Avoidance of CPM/EPM is dependent upon recognizing those patients with conditions pre-disposing them to osmotic myelinolysis and then moderating the rate of normalization of the electrolyte imbalance. The morbidity and mortality of CPM/EPM has been greatly reduced by recognition of pre-disposing conditions, increased understanding of the pathophysiology, intensive treatment, and rapid diagnosis and monitoring with advanced neuroimaging.

Animals↗

Concomitant choroid plexus papillomas involving the third and fourth ventricles: A case report and review of the literature.

Choroid plexus papillomas (CPP) are histopathologically benign and rare central nervous system (CNS) neoplasms arising from the epithelium of the choroid plexus. The most common site of presentation of these lesions is in the fourth ventricle in adults and lateral ventricles in children. Third ventricular CPP are uncommon. In this study, we present a case of a 66-year-old woman with complaints of progressive confusion, lethargy, and weakness who was found to have concomitant third and fourth ventricular masses on imaging studies. The patient underwent a biopsy of the third ventricular mass. The biopsy was followed by staged resections of the fourth and third ventricular masses, respectively. Pathology from the biopsy and both resections was benign CPP. Multifocal concomitant CPP is rare. Concomitant CPPs may be secondary to mere coincidental tumor occurrence or to biologic seeding of cerebrospinal fluid (CSF) from a primary CPP despite otherwise benign histopathology. The primary treatment for CPP is surgical resection. Post-operative chemotherapy or radiation for CPP is of controversial benefit.

Aged↗

Expression of eukaryotic initiation factor 4E in astrocytic tumors.

Upregulation of expression of the eukaryotic initiation factor 4E (eIF4E) has been identified in breast carcinomas, squamous cell carcinomas in the head and neck regions, and transitional cell carcinomas of urinary bladder. In this immunohistochemical study, eIF4E protein expression was investigated in human brain tissue from patients without central nervous system diseases and brain biopsy tissues from patients with anaplastic astrocytoma and glioblastoma multiforme. Expression of eIF4E protein was observed in normal pyramidal neurons but not in neuroglial components. In anaplastic astrocytoma and glioblastoma multiforme, there was diffuse uniform expression of eIF4E immunoreactivity in malignant astrocytes. A similar pattern of immunoreactivity was also present in proliferative endothelial cells and vascular lining endothelial cells in glioblastoma multiforme. This study provides evidence that eIF4E is upregulated in high-grade astrocytic tumors. As in other malignancies, a high level of eIF4E may play an important role in the neoplastic transformation, angiogenesis, and tumor growth in astrocytic tumors. Because eIF4E is crucial in regulation of tumor growth, eIF4E could be a potential target for inhibitors as an adjuvant therapy for brain tumors.

Astrocytoma↗

Anaplastic thyroid cancer and hyperthyroidism.

We report a rare case of thyrotoxicosis in a patient with anaplastic thyroid cancer. A 65-yr-old male presented with a 2-d history of rapidly enlarging neck mass and back pain. Physical examination revealed a large, hard thyroid mass and resting tachycardia. He did not have any symptoms suggestive of airway compression at presentation. Thyroid hormone levels were consistent with a hyperthyroid state. CT scan of the neck and thorax showed a heterogeneous mass replacing the thyroid, bilateral pulmonary nodules, and a metastasis with pathological fracture at the level of T-8. Technetium-pertechnetate scan failed to show any uptake in the region of the thyroid. Fine needle aspiration of the thyroid revealed anaplastic thyroid cancer. The patient was started on steroids and radiation therapy of his spine lesion. Brief surgical exploration of the thyroid revealed extensive local infiltration of adjacent neck tissues and marked tumor necrosis. Immunohistochemical stains of the tumor were positive for p53, thyroglobulin, and thyroid transcription factor-1. The tumor had an extremely aggressive course and the patient died of asphyxiation from severe airway compromise 11 d after his initial presentation.

Aged↗

Metastatic lesions involving the sella: report of three cases and review of the literature.

Metastatic cancer must be considered as a possibility for intrasellar masses. Newer treatment modalities, such as gamma knife radiosurgery needs to be explored for these lesions. Three cases of intrasellar metastatic lesions were retrospectively reviewed. Presenting complaints, radiographic studies, operative procedure, and histopathological confirmation were recorded for each patient. All had an unknown primary malignancy prior to the presentation with the intrasellar lesion detected by magnetic resonance imaging (MRI). Presenting symptoms were diplopia with extraocular movement deficits in all patients. Transsphenoidal resection or biopsy was performed. Histopathological analysis revealed small cell carcinoma in two patients and plasmacytoma in one. All patients received postoperative radiation and/or chemotherapy. Survival following initial presentation was 2 months and 6 months for two of the patients; the third patient is alive at 2-month follow-up.

Aged↗

Solitary tuberculoma of the cerebellopontine angle: a rare presentation.

Central nervous system tuberculoma presenting as a solitary mass in an extrinsic location is rare. Due to the increase in incidence of tuberculosis in the western world, there is a corresponding increase in CNS tuberculosis. Cerebellopontine angle tumours are most commonly acoustic schwannomas or meningiomas. Radiosurgery as a primary modality of treatment for many CNS masses without prior pathological diagnosis is increasing in popularity. This report shows that a mass in the CP angle can closely mimic a tumour radiologically and inappropriate radiation treatment was avoided after surgery. Histopathological examination proved it to be a tuberculoma. Awareness of this rare presentation of a solitary tuberculoma in the CP angle is emphasised.

Brain Neoplasms↗

Cyclooxygenase-2 expression in brain metastases.

BACKGROUND: Elevated Cyclooxygenase-2 (COX-2) expression is thought to increase metastatic potential of many tumors. Furthermore, elevated COX-2 expression correlates with radiation resistance in many tumor types. We evaluated whether: (i) the degree of COX-2 expression correlated with either metastatic tumor type or with the presence of necrosis and whether (ii) radiation-resistant tumors (renal cell and melanoma) had higher expression of COX-2 than did relatively radiation-sensitive tumors (breast and lung). MATERIALS AND METHODS: Specimens from sixteen patients who underwent resection of brain metastases were analyzed for COX-2 expression using a COX-2 antibody-based immunoassay. Specimens consisted of brain metastases from lung tumors, breast adenocarcinomas, melanomas and renal cell carcinomas. All specimens were analyzed for the presence or absence of necrosis. RESULTS: Ten of sixteen brain metastasis specimens had ten percent or less Cox-2 immunostaining. Statistical analyses showed no correlation between Cox-2 immunostaining and metastatic tumor type or between Cox-2 immunostaining and necrosis in this study. Furthermore, renal cell carcinoma and melanoma showed variable Cox-2 immunostaining. CONCLUSION: Cox-2 is not consistently expressed in metastases to the brain. The degree of Cox-2 expression does not correlate with metastatic tumor type or with the presence of necrosis. Radioresistant tumors did not have statistically different expression of Cox-2 than radiosensitive specimens studied in this analysis.

Adenocarcinoma↗

Fever, chills, and weakness in a 61-year-old man.

A 61-year-old man presented to the emergency department of a community hospital with a 2-week history of fever, chills, and sudden extreme weakness of his right arm and lower extremities. He also had a cough, shortness of breath, nausea, abdominal pain, diarrhea, and myalgia. Though initially alert and cooperative, he quickly became unresponsive. In addition, he had hyponatremia, renal insufficiency, and compromised cardiopulmonary function. He was admitted to the intensive care unit for suspected bacterial infection and was started on broad-spectrum antibiotics. Chest radiograph revealed miliary infiltrates consistent with infectious emboli or metastatic carcinoma. Despite intensive resuscitation, the patient died 36 hours after admission. At autopsy multiple nodular lesions were observed on gross examination of the lungs, perihilar and paratracheal lymph nodes, and liver. Microscopic sections of the lung (Figure 1) and brain (Figures 2 and 3) are shown.

Blastomycosis↗