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2.
AJNR Am J Neuroradiol ; 40(1): 68-73, 2019 01.
Article in English | MEDLINE | ID: mdl-30467220

ABSTRACT

BACKGROUND AND PURPOSE: Chronic hydrocephalus is associated with dilated ventricles despite a normal intracranial pressure. In idiopathic intracranial hypertension, the ventricles are normal despite an elevated intracranial pressure. This apparent paradox has largely remained unexplained. It is suggested that a pressure difference between the superficial and deep venous territories of the brain could account for the variation between the 2 diseases. The purpose of this paper is to investigate the cause of this pressure difference. MATERIALS AND METHODS: Using MR phase-contrast imaging, we calculated the hydraulic diameters of the sagittal and straight sinuses in 21 patients with hydrocephalus, 20 patients with idiopathic intracranial hypertension, and 20 age-matched controls. The outflow resistance of each sinus was estimated using the Poiseuille equation. The outflow pressure was estimated using the flow data. A smaller subset of the patients with hydrocephalus had these studies repeated after successful shunt insertion. RESULTS: In hydrocephalus, the sagittal sinuses were 21% smaller than those in controls (P < .001); the straight sinuses were not significantly different. In idiopathic intracranial hypertension, both sinuses were not significantly different from those of controls. The pressure drop from the sagittal sinus to the end of the straight sinus was elevated by 1.2 mm Hg in hydrocephalus (P = .001) but not significantly different from that in controls in idiopathic intracranial hypertension. Shunt insertion dilated the sagittal sinuses in hydrocephalus, leaving them 18% larger than normal and eliminating the transvenous pressure change. CONCLUSIONS: There is a transvenous pressure difference in hydrocephalus that is absent in idiopathic intracranial hypertension. This difference is eliminated by shunt insertion. The findings may have a bearing on ventricular dilation.


Subject(s)
Cranial Sinuses/physiopathology , Hydrocephalus/physiopathology , Pseudotumor Cerebri/physiopathology , Adult , Cranial Sinuses/diagnostic imaging , Female , Humans , Intracranial Pressure/physiology , Male , Middle Aged , Young Adult
3.
Ann R Coll Surg Engl ; 93(7): e129-30, 2011 Oct.
Article in English | MEDLINE | ID: mdl-22004620

ABSTRACT

Although much is known about the late intestinal side effects of radiation, comparatively little has been published about its acute complications. We present a case of a small bowel obstruction due to acute radiation enteritis. As radiotherapy continues to expand its role in the management of oncological disease, clinicians should remain alert to the resulting undesired effects.


Subject(s)
Enteritis/etiology , Intestinal Obstruction/etiology , Intestine, Small/radiation effects , Radiation Injuries/complications , Aged , Gastrointestinal Hemorrhage/etiology , Humans , Male , Prostatic Neoplasms/radiotherapy , Radiotherapy/adverse effects
4.
J Urol ; 166(4): 1220-33, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11547047

ABSTRACT

PURPOSE: Locally advanced, relapsed and metastatic prostate cancer has a dismal prognosis with conventional therapies offering no more than palliation. In recent years advances achieved in understanding the molecular biology of cancer have afforded clinicians and scientists the opportunity to develop a range of novel genetic therapies for this disease. MATERIALS AND METHODS: We performed a detailed review of published reports of gene therapy for prostate cancer. Particular emphasis was placed on recent developments in the arena of nonviral (plasmid DNA, DNA coated gold particles, liposomes and polymer DNA complexes) and viral (adenovirus, retrovirus, adeno-associated virus, herpes virus and pox virus) vectors. Therapeutic strategies were categorized as corrective, cytoreductive and immunomodulatory gene therapy for the purpose of data analysis and comparison. RESULTS: Locoregional administration of nonviral and viral vectors can yield impressive local gene expression and therapeutic effects but to our knowledge no efficient systemically delivered vector is available to date. Corrective gene therapy to restore normal patterns of tumor suppressor gene (p53, Rb, p21 and p16) expression or negate the effect of mutated tumor promoting oncogenes (ras, myc, erbB2 and bcl-2) have efficacy in animal models but this approach suffers from the fact that each cancer cell must be targeted. A wide variety of cytoreductive strategies are under development, including suicide, anti-angiogenic, radioisotopic and pro-apoptotic gene therapies. Each approach has strengths and weaknesses, and may best be suited for use in combination. Immunomodulatory gene therapy seeks to generate an effective local immune response that translates to systemic antitumor activity. Currently most studies involve immunostimulatory cytokine genes, such as granulocyte-macrophage colony-stimulating factor, or interleukin-2 or 12. CONCLUSIONS: Various therapeutic genes have proved activity against prostate cancer in vitro and in vivo. However, the chief challenge facing clinical gene therapy strategies is the lack of efficient gene delivery by local and systemic routes. For the foreseeable future vector development may remain a major focus of ongoing research. Despite this caveat it is anticipated that gene therapy approaches may significantly contribute to the management of prostate cancer in the future.


Subject(s)
Genetic Therapy/methods , Prostatic Neoplasms/therapy , Adjuvants, Immunologic , DNA , Forecasting , Genetic Therapy/trends , Genetic Vectors , Humans , Male , Prostatic Neoplasms/genetics
5.
Expert Opin Investig Drugs ; 9(12): 2799-813, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11093354

ABSTRACT

Cancer, at the molecular level, continues to be more thoroughly understood. With this understanding comes the opportunity for innovative therapeutic intervention. Gene therapy remains an attractive concept to treat cancer. However, a number of gene therapy clinical trials have now been reported and it is clear that barriers remain before gene therapy gains widespread clinical application. This article outlines current directions and novel developments in the field of cancer gene therapy, which attempt to overcome these obstacles.


Subject(s)
Genetic Therapy/trends , Neoplasms/therapy , Animals , Genetic Therapy/methods , Humans , Neoplasms/pathology
6.
Ann Oncol ; 8(7): 669-73, 1997 Jul.
Article in English | MEDLINE | ID: mdl-9296220

ABSTRACT

BACKGROUND: Cancer patients frequently suffer thromboembolic events. This study assessed the incidence and resource implications of cancer-related thromboembolic disease (CTD) in a single, large cancer centre. PATIENTS AND METHODS: A retrospective analysis of patients admitted with CTD and/or the complications of treatment of CTD over a two-year period has been conducted. Forty-eight patients (23 male, 25 female, median age 60 years) with a variety of solid tumours were identified. RESULTS: The initial presentations were venous thromboses (28 patients) and pulmonary embolism (20 patients). The median interval from cancer diagnosis to the initial episode of CTD was eight (range 0-112) months. Twenty-two patients suffered additional thromboses, despite maintenance warfarin anticoagulation in 18 patients. Six patients experienced anticoagulation-induced haemorrhage. Forty-one (85.4%) patients have died. The median survival from the first thromboembolic event was 8.5 months. The median inpatient stay for management of the first event was 10 (range 4-75) days, accounting for 729 inpatient days during the study period. Recurrent episodes of CTD or complications of anticoagulation resulted in 28 readmissions, accounting for 295 inpatient days. During the two-year period 1024 inpatient days were directly caused by CTD and its complications, representing 6.1% bed occupancy on our unit. CONCLUSION: This study demonstrates that CTD represents a significant cause of morbidity in cancer patients with considerable resource implications for cancer centres. Improvements in prevention and management of CTD would reduce morbidity and lead to considerable cost savings.


Subject(s)
Neoplasms/complications , Thromboembolism/epidemiology , Adult , Aged , Aged, 80 and over , Anticoagulants/therapeutic use , Female , Humans , Male , Middle Aged , Neoplastic Cells, Circulating , Retrospective Studies , Thromboembolism/mortality , Thromboembolism/therapy
7.
Clin Oncol (R Coll Radiol) ; 7(6): 373-6, 1995.
Article in English | MEDLINE | ID: mdl-8590699

ABSTRACT

The purpose of this study was to identify risk factors for pneumothorax during percutaneous subclavian Hickman line insertion in patients with haematological (HT) or solid tumours (ST). One hundred and twelve patients (55 HT, 57 ST) had 132 subclavian Hickman lines inserted under fluoroscopic control. Lines were inserted on the left on 116 occasions and the right in 16. Thirty-five single, 29 double and 68 triple lumen catheters were inserted. Variables included in the analysis were age, sex, side of insertion, catheter gauge and nutritional status as indicated by the body mass index (BMI kg/m2). Both univariate and logistic regression analyses were performed. There were ten pneumothoraces, all occurring in patients with STs. Univariate analysis revealed that patients with STs were older (median age 59 versus 36 years; P = 0.0001) and more cachectic (median BMI 21.9 versus 24.2 kg/m2; P = 0.03) than those with HTs, and the patients experiencing pneumothorax were older (median age 57 versus 44 years; P < 0.01) and more cachectic (median BMI 19.6 versus 24.0 kg/m2; P = 0.004) than those undergoing uncomplicated procedures. For patients with a BMI < 19 kg/m2 versus those with a BMI > 19 kg/m2, the pneumothorax rate was 5/8 versus 5/124 (P < 0.00001). Logistic regression analysis confirmed the significantly older age of the patients with STs (P < 0.001) and of those experiencing pneumothorax (P = 0.02). This analysis also confirmed the lower BMI of patients experiencing pneumothorax (P = 0.002). The patients' sex, the side of line insertion and the catheter gauge were not associated with pneumothorax on either the univariate or logistic regression analyses. From these data we conclude that pneumothorax complicating a subclavian Hickman line is significantly more likely in elderly patients with a low BMI. Such patients are more likely to have STs than HTs. In patients with a BMI < 19 kg/m2, the subclavian route should be used with caution.


Subject(s)
Catheterization, Peripheral/adverse effects , Leukemia/therapy , Neoplasms/therapy , Pneumothorax/etiology , Adult , Catheterization, Peripheral/methods , Female , Humans , Leukemia/complications , Logistic Models , Male , Middle Aged , Neoplasms/complications , Retrospective Studies , Risk Factors , Subclavian Artery
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