Postsynaptic factors in the expression of long-term potentiation (LTP): increased glutamate receptor binding following LTP induction in vivo.

Several lines of evidence indicate that LTP in the hippocampus is associated with a change in the properties of postsynaptic glutamate receptors. In the present study, we used quantitative autoradiography to examine the binding properties of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA) and N-methyl-D-aspartate subclasses of glutamate receptors in frozen brain sections obtained from rats in which perforant-path LTP was induced in vivo. Induction of LTP resulted in a selective increase in [3H]AMPA binding in those hippocampal subfields receiving perforant-path axons. Increases in [3H]AMPA binding in dentate gyrus (stratum moleculare) were highly correlated with the magnitude of LTP recorded in this structure. Scatchard analyses of [3H]AMPA and 6-cyano-7-nitro-[3H]quinoxaline-2,3-dione (an AMPA receptor antagonist) binding in the dentate gyrus indicated that LTP induction resulted in an increase in the number of AMPA receptor binding sites. No changes in the binding of 3H-labeled N-[1-(thienyl)cyclohexyl]piperidine (an N-methyl-D-aspartate receptor antagonist) were observed in any hippocampal subfield. These results suggest that a modification in postsynaptic AMPA receptors plays a role in the expression of synaptic enhancement following LTP induction in the hippocampus.     

Enlargement of the blind spot caused by papilledema

Blind spot enlargement in papilledema has been attributed to either mechanical disruption of the integrity of the peripapillary percipient elements by the swollen optic disk or to the Stiles-Crawford effect. We investigated the possibility that blind spot enlargement in papilledema is caused, at least in part, by a refractive scotoma due to peripapillary hyperopia. We reduced the enlarged blind spot in a patient with focal peripapillary hyperopia, without papilledema, to near normal size by using progressively stronger plus lenses. Similarly, with the addition of plus sphere, we reduced the size of the blind spot in five of six patients with papilledema, but in none of our normal subjects.     

Postoperative pulmonary toxicity associated with mitomycin-C therapy.

As more patients survive cancer, and as more sophisticated multidrug antineoplastic protocols are developed, the chances of an anesthesiologist's coming into contact with patients who have been treated with such protocols are increasing. The anesthesiologist who must administer anesthesia to a patient who has had chemotherapy must be cognizant of the particular antineoplastic agents that have the potential for producing occult pulmonary dysfunction. Anesthetic management of these cases must be carefully planned and titrated to prevent further lung injury.     

Ankylosing spondylitis antirheumatic drug trials. III. Setting the delta for clinical trials of antirheumatic drugs--results of a consensus development (Delphi) exercise.

Defining the minimum clinically important difference or delta to be detected in a clinical trial depends on a number of factors including the research hypothesis, patient characteristics, the nature of the intervention and the trial design. In 2 previous studies, we have developed standardized procedures for conducting outcome measurement based on current Food and Drug Administration and European League Against Rheumatism guidelines for clinical trials in ankylosing spondylitis, and thereafter, determined the standard deviation for these outcome measures. In the final component of this series of studies, we have employed a Delphi technique to establish estimates for delta, and calculated the sample size requirements under 2 different conditions of Type I and Type II error probabilities.     

Flaxseed supplementation and early markers of colon carcinogenesis.

Since flaxseed ingestion produces potentially anticarcinogenic lignans in the colon, this study determined whether flaxseed decreases the risk for colon carcinogenesis. Following a single injection of azoxymethane (15 mg/kg body wt.), five groups of male Sprague-Dawley rats were fed a high-fat (20% corn oil) basal diet with or without supplementation with 5% or 10% flaxseed meal (FM) or flaxseed flour (FF) for four weeks. Upon sacrifice, colons were examined for aberrant morphology and cell proliferation. In the descending colon of supplemented groups, the total number of aberrant crypts and foci were significantly reduced by 41-53% and 48-57%, respectively. The labeling index (LI) was also 10-22% lower in these groups, except for the 5% FM group. While these effects are not linearly related to the level of flaxseed fed, it suggests that flaxseed feeding may reduce the risk for colon carcinogenesis.     

Peroneal nerve palsy after early cast application for femoral fractures in children.

The incidence and contributing factors associated with post-casting peroneal nerve palsy were examined in a series of 110 consecutive pediatric femoral shaft fractures treated with early hip spica cast application. Four patients with peroneal nerve palsy were identified. All four had 90 degrees/90 degrees casts placed and underwent cast wedging for alignment. All palsies resolved with immediate cast removal. Other treatment options for certain femur fractures with significant initial shortening should be considered. We advise pre- and post-cast neurologic examination and avoidance of forceful distraction. Fracture manipulation, through wedging, should be delayed.     

The fate of buried vaginal epithelium.

A new technique in the treatment of stress urinary incontinence utilizes a sling fashioned from a rectangular island of buried vaginal epithelium. We developed a model to study the natural history of vaginal wall covered by an epithelial flap in 12 rabbits sacrificed at intervals to 26 weeks. Histopathologic examination demonstrated an immediate acute inflammatory reaction. This early response was followed by formation of an epithelial lining of the potential space overlying the buried vaginal tissue. Acute inflammatory cells continued to enter this lumen until week 20, when granulomas were first detected. Histopathologic examination at twenty-six weeks showed stratified squamous epithelium lining the lumen. No deleterious inflammatory sequelae were detected, and no dysplastic or malignant changes were identified. These results suggest that buried vaginal epithelium is a safe (short term) tissue alternative for sling creation.     

Role for interleukin-1 (IL-1) in benzene-induced hematotoxicity: inhibition of conversion of pre-IL-1 alpha to mature cytokine in murine macrophages by hydroquinone and prevention of benzene-induced hematotoxicity in mice by IL-1 alpha

Chronic exposure of humans to benzene (BZ), a myelotoxin, causes aplastic anemia and acute leukemia. The stromal macrophage that produces interleukin-1 (IL-1), a cytokine essential for hematopoiesis, is a target of BZ's toxicity. Monocyte dysfunction and decreased IL-1 production have been shown to be involved in aplastic anemia in humans. Hydroquinone (HQ), a toxic bone marrow (BM) metabolite of BZ, causes time- and concentration-dependent inhibition of processing of the 34-Kd pre-interleukin-1 alpha (IL-1 alpha) to the 17-Kd mature cytokine in murine P388D1 macrophages and BM stromal macrophages, as measured by Western immunoblots of cell lysate proteins using a polyclonal rabbit antimurine IL-1 alpha antibody. HQ over a 10-fold concentration range had no effect on the lipopolysaccharide (LPS)-induced production of pre- IL-1 alpha precursor or on cell viability or DNA and protein synthesis. Stromal macrophages obtained from the femoral BM of C57Bl/6 mice exposed to BZ (600 or 800 mg/kg body weight) for 2 days were incapable of processing the 34-Kd pre-IL-1 alpha to the mature 17-Kd cytokine when stimulated in culture with LPS. Stromal macrophages from mice coadministered BZ and indomethacin, a prostaglandin H synthase (PHS) inhibitor that has been shown to prevent BZ-induced myelotoxic and genotoxic effects in mice when coadministered with benzene were able to convert the pre-IL-1 alpha to mature cytokine. Administration of recombinant murine IL-1 alpha (rMuIL-1 alpha) to mice before a dose of BZ that causes severe depression of BM cellularity completely prevents BM depression, most probably by bypassing the inability of the stromal macrophage in BZ-treated animals to process pre-IL-1 alpha to the mature cytokine.