Faculty Bibliography

The application of a monoclonal antibody to bromodeoxyuridine (BUdR) provides a rapid, reproducible, nontoxic, immunohistochemical method to measure cellular kinetics of intracerebral tumor angiogenesis. The rabbit brain tumor model of angiogenesis consists of tumor and endothelial cell populations with high proliferative rates that demonstrate the close interdependence between microvascular and neoplastic growths as well as topographic gradients, heterogeneity, and regional microdomains of cell proliferation. The labeling index (LI) of endothelial cells was 25.8% at the tumor periphery, compared to 1.7% in the tumor center (P less than 0.001). Concomitant with an increased turnover of neoplastic cells at the tumor periphery. LI was 26.6% with a LI of 7.7% in the center (P less than 0.01). Furthermore, labeled tumor cells tended to be organized around proliferating capillaries, with less DNA synthesis farther from the nearest blood vessel. The established normal microvessels of the brain, e.g., in the opposite tumor-free hemisphere, were mitotically inactive with a LI of less than 0.001%. Quantitation of vascular cytokinetics should be useful in further studies of the pathophysiology of brain tumor angiogenesis and the development of pharmacological approaches directed toward the microvasculature

Because of the crucial role played by tumor neovascularization in contrast enhancement, we studied the CT imaging findings in a transplantable rabbit brain tumor, the VX2 carcinoma that induces angiogenesis and the breakdown of blood-brain barrier associated with contrast enhancement. Tumor detection by contrast enhancement followed the peak of angiogenesis. Inhibition of angiogenesis, by copper depletion and penicillamine, led to avascular tumors that lack contrast enhancement. Furthermore, there was no contrast enhancement in brain adjacent to the tumor of normocupremic rabbits or within the hypocupremic tumor, despite the breakdown of the blood-brain barrier, without the concomitant presence of angiogenesis. We conclude that contrast enhancement of intracranial tumors is dependent primarily on the proliferation of the microvasculature

A model for the study of tumor angiogenesis within the rabbit brain is presented. Implantation of the VX2 carcinoma provides a reproducible tumor accompanied by angiogenesis. The authors report the sequential growth, histology, tumor neovascularization, and vascular permeability of this tumor following its intracerebral implantation. Tumor angiogenesis correlates with the rapid and logarithmic intracerebral tumor growth. The proliferation of blood vessels in the tumor and the organization of tumor cells around tumor vessels are described. Breakdown of the blood-brain barrier (detected by Evans blue leakage) starts in the early stages of tumor development and becomes prominent as the tumor vasculature and size increase. This model is useful for experimental studies of angiogenesis

A randomized, placebo-controlled, double-blind and sequentially analysed clinical trial to determine the efficacy of intra-operative parenteral gentamicin and vancomycin (with streptomycin in the irrigating solution) in preventing infection at the operative site following neurosurgical procedures is described. Patients receiving prophylaxis had a significantly (P = 0.046) lower operative site infection rate (2/71 = 2.8%) than those receiving placebo (9/77 = 11.7%). This difference was most apparent during an epidemic, the source of which was not evident. Moreover, a total of 13 infections (two operative site, five pneumonia and six urinary tract) occurred among 12 patients receiving prophylaxis, whereas there was a total of 31 infections (nine operative site, nine pneumonia, 10 urinary tract and three septicaemia) among 24 patients receiving placebo. A smaller quantity of antimicrobial drugs was administered postoperatively to patients receiving prophylaxis (3.96 'antibiotic-days' per patient) than to those receiving placebo (6.87 'antibiotic-days' per patient).

Autotomy in nerve injured rats has been put forward as an animal model in a broad range of chronic neuralgic pain. We have examined the effect of glycerol, a new and promising therapeutic agent for trigeminal neuralgia, on this animal model. A single dose of glycerol, alcohol or saline was injected directly into experimental sciatic nerve neuromas in rats via a chronically implanted cannula. Injections were made either at the time of nerve injury or 2 weeks afterwards. Both forms of glycerol treatment caused a significant reduction in autotomy behavior relative to saline. Alcohol also suppressed autotomy, but it was less effective than glycerol.

Percutaneous chemical lumbar sympathectomy with alcohol (PCLSA) using computed tomography (CT) control was performed in 8 patients suffering from advanced peripheral arterial occlusive disease. PCLSA under CT guidance was found to be a simple and safe procedure. The use of CT control added precision in the guidance of needle placement. Positive results were obtained in all patients, without significant morbidity. PCLSA may be an alternative to surgical sympathectomy.

The case of an asymptomatic 7-year-old girl with a hard bulge in the left forehead is presented. The radiological evaluation disclosed a hyperostotic mass with a large intracranial extension. A surgical specimen revealed a meningioma. The presence of a localized cranial bulge as the only sign of an intracranial tumor and the diagnostic value of computerized tomography (CT) are discussed.

Autotomy has been suggested as an animal model of chronic pain. It starts about a week or two postoperatively and develops until 10 weeks after nerve section. This behaviour is thought to be triggered by activity of sensory fibres ending in a neuroma. Here we suggest to utilize it in combination with a novel drug delivery system which enables a direct and exclusive access of the drug to the neuroma. Alteration in the autotomy behaviour can then be related to the exclusive topical action on the sensory fibres within the neuroma. The sciatic nerve is transsected and its proximal end inserted into a PE tube sealed distally. A second, smaller tube originates in a wound exit in the back of the animal and subcutaneously leads into the large tube, where it is fixed by glue to the inner wall. Thus, the end of the smaller tube is juxtaposed to the nerve end. During the following weeks a neuroma develops within the tube. The resulting autotomy scores are then examined weekly. At various times after the operation, under light anaesthesia, drugs can be injected into the tube and the effect on the autotomy behaviour is monitored. An example is given, describing the autotomy suppressive effects of glycerol and alcohol, injected to different groups of rats immediately after the operation and compared to an injection 14 days postoperatively. This method is suggested as a pharmaco-behavioural assay for the assessment of the analgetic efficacy of drugs for chronic pain.