The response of spontaneous and transplantable murine tumors to vasoactive agents measured by 31P magnetic resonance spectroscopy.

31P magnetic resonance spectroscopy has been used to compare the effects of the vasoactive agents hydralazine and flunarizine on the oxygenation of the transplantable tumors, SCCVII/Ha and 16C, and a range of spontaneous mammary tumors arising in the breeding stock in the Genetics Division at the Radiobiology Unit. The vasodilator hydralazine, previously shown to increase the radiobiological hypoxic fraction of transplantable murine tumors, increased inorganic phosphate to total phosphate (Pi/total) in SCCVII/Ha and 16C tumors. However, only two spontaneous tumors responded to this agent (2/12). The calcium antagonist flunarizine, which sensitizes the SCCVII tumor to X rays, consistent with a reduction in hypoxic fraction, reduced Pi/total in this and the 16C tumor. Further, most spontaneous tumors tested (8/10) responded to this agent, as measured by a reduction in Pi/total. These results point to fundamental differences between transplantable and spontaneously arising tumors in mice in their response to vasoactive agents.     

Gd DTPA. Future applications with advanced imaging techniques

In this admittedly preliminary view of the future, the authors present a number of new concepts in MR imaging and consider their possible advantages and limitations.     

DQ Wa gives rise to a DQβ restriction fragment pattern indistinguishable from that of the DQw3.2 sub-type Of DQw3

DQ beta restriction fragment patterns have been obtained from five DRw8 cell lines homozygous for the null DQ allele, DQWa. The enzymes Bgl II, Bam HI and Pvu II generate DQ beta patterns which are indistinguishable from those obtained from cell lines homozygous for DQw3.2.     

Distribution of retroperitoneal metastases after chemotherapy in patients with nonseminomatous germ cell tumors.

For patients with advanced nonseminomatous germ cell tumors a retroperitoneal lymph node dissection is routinely performed following chemotherapy if the serum tumor markers have returned to normal. Bilateral retroperitoneal lymph node dissection has been recommended because metastatic deposits may be widespread. The aim of this study was to describe the distribution of retroperitoneal metastases following chemotherapy in patients with nonseminomatous germ cell tumor and determine if the extent of the retroperitoneal lymph node dissection can be modified. We studied 113 patients who had initially bulky retroperitoneal disease and underwent retroperitoneal lymph node dissection following chemotherapy. For the purposes of this study teratoma and malignant germ cell tumor are referred to as tumor. The most common location of tumor was the para-aortic area (91%) in patients with a left primary tumor and the interaortocaval area (78%) in those with a right tumor. Tumor was located outside the boundaries of a modified retroperitoneal lymph node dissection in 14 of the 60 patients with residual disease but the tumor was present within a palpable mass in 6 of these 14 patients. If the residual mass was removed and a modified retroperitoneal lymph node dissection was performed only 9 of the 113 patients (8%) would have tumor left in the retroperitoneum. For a select group of patients with advanced nonseminomatous germ cell tumor treated with chemotherapy, resection of the residual mass combined with modified retroperitoneal lymph node dissection is appropriate.     

Types of anterior cervical grafts.

Anterior cervical diskectomy and fusion provide satisfactory results in most instances of cervical disk herniation and cervical spondylosis. A variety of interpositioned grafts have been described for such problems at one or two levels. Multiple level anterior decompression and fusion for patients with spondylotic myelopathy produce satisfactory results in most instances and are particularly effective when a degenerative kyphosis is present. Appropriate patient selection and attention to technical aspects of exposure, neural decompression, and graft procurement and placement directly influence the surgical outcome.     

Invited review: Neuroprotective properties of certain beta-adrenoceptor antagonists used for the treatment of glaucoma.

Although it is known that ganglion cell death causes loss of vision in glaucoma, the pathogenesis of the disease is complex, probably involving an initial ischemic insult to the ganglion cell axons and glial cells with the ganglion cell bodies eventually being affected. It may therefore be necessary to blunt many stages in the pathogenesis of the disease to obtain a clinically effective neuroprotective strategy. In animal experiments, one cause of ganglion cell death in ischemia is an overactivation of glutamate receptors and a subsequent rise in intracellular levels of sodium and calcium ions as well as a generation of reactive oxygen species. In contrast, optic nerve death in ischemia is mainly caused by an influx of sodium and reversal of the sodium/calcium exchanger, which leads to a rise in intracellular calcium. Thus, a substance that reduces the influx of sodium will protect the ganglion cell axon, and if it also reduces calcium influx and/or acts as an antioxidant it will protect the ganglion cell body in addition. Of all antiglaucoma drugs, only beta-blockers have both calcium and sodium channel blocking activity, with betaxolol being the most efficacious of those analyzed. In addition, of the tested ophthalmic beta-blockers only metipranolol has powerful antioxidant properties. Moreover, laboratory studies on rats have shown that topically applied beta-blockers attenuate ischemic injury to ganglion cells by mechanisms that do not appear to involve an action on beta-receptors. Thus, of the substances used to lower intraocular pressure in glaucoma, beta-blockers have unique additional characteristics that also give them the capacity to act as neuroprotectants.     

p53-related pathways and the molecular pathogenesis of melanoma.

Cutaneous malignant melanoma (CMM) is a life-threatening cancer that can have a poor prognosis with high metastatic potential. Its incidence is rapidly increasing worldwide. Its molecular alterations involve multiple pathways, including those related to p53. Since 1981, more than 380 papers containing the terms 'p53 and melanoma' as key words in the Abstract have been published in the literature. However, in spite of these extensive investigations, a review of p53 and associated genes in CMM is still lacking. To remedy this issue, this review seeks to provide a brief overview of p53 and discuss the genes targeted along its related pathways.     

Guidelines for the collection, processing and storage of human bone marrow and peripheral stem cells for transplantation

SUMMARY. There are no current U.K. or international guidelines or regulations covering the production, processing and storage of haemopoietic cells such as to allow their engraftment following myeloablative therapy. This paper seeks to provide such guidelines. It enumerates how quality control and assurance can be applied to this area of transfusion medicine; procedural steps relating to bone marrow harvest on peripheral blood stem cell collection are outlined and recommended doses of nucleated cells suggested for both procedures. General specifications for identification, storage and transportation of bone marrow and peripheral blood stem cells are included and specific laboratory procedures related to the provision of haemopoietic cells for engraftment are outlined. Umbilical cord blood transplants and long-term bone marrow culture are alluded to but these are still in a research phase.