Assessment of closed head injury in trauma-related spinal cord injury

The complete medical records of 122 patients who sustained traumatic spinal cord injuries were reviewed to determine the frequency and results of emergency room assessments for loss of consciousness (LOC) and post-traumatic amnesia (PTA). Eighty-eight percent of the patients were assessed for LOC and 19% were assessed for PTA. Fifty patients (41% of the total population) admitted to LOC, PTA or both. Fourteen of these 50 patients underwent subsequent radiographic examinations of the skull, all of which were negative. Because of the association of intracranial complications and long-term cognitive sequelae with even brief LOC or PTA, early recognition of craniocerebral trauma is an important component of the acute management of spinal cord injured patients.     

CT of the pancreas with a fat-density oral contrast regimen

Visualization of the head of the pancreas by CT was prospectively evaluated in two groups of 100 patients who did not have pancreatic disease. Patients were given either a fat-density oral contrast material (12.5% corn-oil emulsion and metoclopramide) or a conventional high-density oral contrast material (barium suspension or iodinated solution). There was no statistically significant difference in the subjects' tolerance to the two regimens. There was, however, a significant improvement in ability to distinguish the head of the pancreas from the duodenal C-loop when the fat-density contrast material was given. When pancreaticoduodenal discrimination was graded, patients given corn-oil emulsion and metoclopramide received an average score of 0.94, whereas those given the high-density agent received an average score of 0.74, with 1.00 being the highest possible score (p less than .005). These data suggest that for routine CT evaluation of the head of the pancreas, a combination of corn-oil emulsion and metoclopramide may be superior to the conventional high-density oral contrast agents given without metoclopramide.     

Adeno-associated virus vector-mediated systemic delivery of IFN-beta combined with low-dose cyclophosphamide affects tumor regression in murine neuroblastoma models.

PURPOSE: Type I IFNs (IFN-alpha/beta) have shown significant antitumor activity in preclinical models but limited efficacy and significant toxicity in clinical trials. We hypothesized that the antitumor activity of type I IFNs could be enhanced by chronic, low-dose systemic delivery and sought to test this in murine neuroblastoma models. EXPERIMENTAL DESIGN: Continuous liver-generated expression of human IFN-beta (hINF-beta) was achieved through a gene therapy-mediated approach using adeno-associated virus vectors encoding hIFN-beta (AAV hINF-beta). Orthotopic localized retroperitoneal and disseminated models of neuroblastoma were established using three different xenografts. Immunohistochemical analysis and ELISA were used to evaluate the antiangiogenic effect of therapy. RESULTS: The development of both localized orthotopic (retroperitoneal) and disseminated neuroblastoma was prevented in all mice expressing hINF-beta. Continued growth of established retroperitoneal tumors, treated with AAV hINF-beta as monotherapy, was significantly restricted, and survival for mice with established, disseminated disease was significantly prolonged following administration of AAV hINF-beta. Analysis of treated tumors revealed a significant antiangiogenic effect. Mean intratumoral vessel density was diminished and expression of the angiogenic factors vascular endothelial growth factor and basic fibroblast growth factor were both decreased. Finally, combination therapy in which AAV hIFN-beta was used together with low-dose cyclophosphamide resulted in regression of both established retroperitoneal and disseminated disease. CONCLUSIONS: AAV-mediated delivery of hIFN-beta when used as monotherapy was able to restrict neuroblastoma growth due in part to inhibition of angiogenesis. When used in combination with conventional chemotherapy, AAV hIFN-beta was able to effect complete tumor regression.     

Unexpected cytokinetic effects induced by puromycin include a G2-arrest, a metaphase-mitotic-arrest, and apoptosis.

The potent effects of low doses of PM on the cell cycle have to date been obscured by the conventional usage of this drug at high concentrations (5-50 micrograms/ml) to inhibit protein synthesis. In this in vitro study undertaken in a variety of malignant and non-malignant human and murine cell types, we found that low doses of PM (0.1-0.5 microgram/ml) disrupted significant phase-to-phase cell cycle transitions, causing a G2-arrest, a metaphase-mitotic-arrest, and apoptosis. In HL-60 cells these observations were elicited by PM concentrations starting at 0.1 microgram/ml, and were more pronounced at slightly higher PM concentrations, including that (0.5 microgram/ml) which inhibited [14C]leucine incorporation by approximately 20% after one hour, and by approximately 50% after 24 h. A concentration of CHX (0.25 microgram/ml) which was equivalent to 0.5 microgram/ml of PM, both in terms of molarity (0.9 microM) and degree of inhibition of [14C]leucine incorporation, failed to induce similar changes to those induced by PM. This suggests that at these particular concentrations the PM-induced changes were likely to have been related to the different mechanisms of protein synthesis inhibition exerted by these two 'classical' translation inhibitors. PM but not CHX generates nascent peptidyl-PM complexes (PMPs), and we therefore propose that the subsequent intracellular effects exerted by the PMPs may account, in part, for the differential cytokinetic effects elicited by these drugs. The role of PM is currently being evaluated in vivo as a low-dose component of a multidrug chemotherapeutic regimen in which its cell cycle-specific effects could potentially be synergistic with other agents.     

Age-related morphological and morphometrical changes in parvalbumin- and calbindin-immunoreactive neurons in the rat hippocampal formation.

Parvalbumin (PV)- and calbindin (CaBP)-immunostaining in the hippocampal formation of 3-, 11- and 28-month-old Wistar rats was studied using monoclonal antibodies. A quantitative analysis of the densities, cross-sectional areas, length and number of processes of PV-immunoreactive neurons in the hippocampal dentata and CA1 areas of the three age groups was employed. Marked age-related changes in the morphological appearance and in the quantitative parameters characterizing the PV-immunoreactive neurons in both hippocampal regions were observed. The intensity of CaBP-immunostaining of the hippocampal principle cells and interneurons remained the same but the immunoreactive fibers were structurally altered in aging.     

Screening of subjects at high risk for diabetic microangiopathies

Chronic hyperglycemia is the single most important pathogenic factor in the diabetic triad: retinopathy, glomerulopathy and neuropathy. But at equal serum glucose balance, diabetics are not equally at risk of microangiopathy. Hence the importance of timely screening of patients who should be convinced to accept the constraints and risk of perfect serum glucose balance or to whom specific therapy independent from serum glucose balance could be proposed. But at present, there is no genetic or immunologic marker allowing for the individual identification of at risk patients. Attention is thus directed towards factors which may be directly involved in the pathogenesis of diabetic microangiopathy: --Special sensitivity of vascular collagen to protein glycosylation which could be reflected in the involvement of tendon and aponeurotic collagen, --platelet abnormalities of which the exacerbating role appears to be confirmed by the significant efficacy of aspirin in the treatment of nonproliferative retinopathy in insulin-independent diabetics, --rheological abnormalities which might essentially be secondary to chronic hyperglycemia, --hormonal abnormalities, in particular hypersecretion of growth hormone and/or somatomedin C, whose role has long been suspected and could be established by therapeutic trials with new somatostatin analogues. But the most recent advances concern the study of hemodynamic factors. Irreversible organic diabetic microangiopathy is thought to be preceded by a phase of reversible functional microangiopathy, characterized by increased capillary blood flow, vascular dilatation, hyperpermeability and altered regulation of flow. Thus, diabetic glomerulopathy with decreased glomerular filtration is preceded by a phase of renal "hyperfunctioning" and irreversible proteinuria is the outcome of a progressive increase in microalbuminuria, reversible at least while the levels are not too high.(ABSTRACT TRUNCATED AT 250 WORDS)