Incremental benefits of FDG positron emission tomography over CT alone for the preoperative staging of ovarian cancer

OBJECTIVE: The purpose of this study was to determine whether the addition of positron emission tomography (PET) with the radiotracer FDG to cross-sectional imaging, such as CT, increases accuracy in the detection of tumor spread. SUBJECTS AND METHODS. Fifteen patients who were thought to have ovarian cancer on the basis of the results of physical examination, sonography findings, and level of serum cancer antigen 125 were enrolled over an 11-month period. After screening, patients underwent two imaging examinations-abdominopelvic CT and whole-body FDG PET- within 2 weeks before surgery. Also before surgery, staging accuracy was assessed separately using CT with or without FDG PET (which was based on modifications of the International Federation of Gynecology and Obstetrics [FIGO] criteria). The results of the histology and surgery findings were used to assess the accuracy of the scanning findings. RESULTS: Staging revealed stage III disease in seven patients (IIIC, n = 6; IIIB, n = 1), stage II in three (IIC, n = 2; IIB, n = 1), and stage I in five (IC, n = 3; IA, n = 2), according to the FIGO criteria. Although CT staging correlated with postoperative staging in eight (53%) of 15 patients, consensus evaluation of CT with FDG PET staging improved correlation with postoperative staging in 13 (87%) of 15 patients. CONCLUSION: The addition of FDG PET to CT increases accuracy in staging of ovarian cancer.     

Reversible posterior leukoencephalopathy in a patient with Wegener granulomatosis

A 14-year-old girl with rapidly progressive glomerulonephritis was transferred to our hospital because of acute renal failure. A diagnosis of Wegener granulomatosis was made according to the symptom triad of a renal biopsy demonstrating crescentic glomerulonephritis, severe sinusitis, and serological findings of raised proteinase 3 anti-neutrophil cytoplasmic antibody level. In spite of combination therapy with methylprednisolone, cyclophosphamide, and plasma exchange, her renal function gradually deteriorated. Thereafter, she suffered a severe headache and generalized seizures. Brain computed tomography (CT) scan revealed bilateral low-density areas in the parieto-occipital lobes. Magnetic resonance imaging (MRI) disclosed a high-intensity area on T2-weighted images and a low-signal intensity area on T1-weighted images in the same lesion. Follow-up brain CT scan 3 weeks and MRI 2 months after the first studies showed complete resolution of the abnormal lesions, which indicated reversible posterior leukoencephalopathy syndrome. In addition to renal failure, hypertension, and cyclophoshamide, the primary disease may have played a role in the development of this uncommon syndrome in our patient.     

LC/PDA/ESI-MS Profiling and Radical Scavenging Activity of Anthocyanins in Various Berries

Anthocyanin extracts of two blueberries, Vaccinium myrtillus (bilberry)and Vaccinium ashei (rabbiteye blueberry), and ofthree other berries, Ribes nigrum (blackcurrant), Aronia melanocarpa (chokeberry), andSambucus nigra (elderberry), were analyzed by high-performanceliquid chromatography coupled withphotodiode array detection and electrosprayionization - mass spectrometry(LC/PDA/ESI-MS). Both bilberry and rabbiteyeblueberry contained 15 identical anthocyanins withdifferent distribution patterns. Black currant,chokeberry, and elderberry contained 6, 4, and 4 kindsof anthocyanins, respectively. The radicalscavenging activities of these berry extracts wereanalyzed by using 2,2-diphenyl-1-picrylhydrazyl(DPPH). All these extracts showed potent antiradical activities.     

Reliability of intraocular pressure by Tono-Pen XL over amniotic membrane patch in human

PURPOSE: To determine the reliability of Tono-Pen XL in measuring intraocular pressure (IOP) over the amniotic membrane patch in human eyes. METHOD: Ten healthy volunteers (nine males and one female) participated in this study. After topical anesthesia, IOP was measured using the Tono-Pen XL before and after the application of a single-layer amniotic membrane patch in the right eye and double-layer amniotic membrane patch in the left eye. RESULTS: We found no statistical difference between the IOP measured with and without a single layer amniotic membrane (P = 0.808). Nor did we find any statistical difference between the IOP measured with and without double-layer amniotic membrane patch (P = 0.813). The average thickness of the single- and the double-layer amniotic membrane patch measured by pachymetry was 131.9 +/- 31.4 microm (mean +/- SD) and was 246.1 +/- 69.3 microm (mean +/- SD), respectively. CONCLUSIONS: This study showed that it is reliable to measure IOP by Tono-Pen XL over single or a double layer of amniotic membrane patch on healthy human eyes. Further studies are required to determine the accuracy of IOP measurement over amniotic membrane patch on diseased corneas.     

Human neural stem/progenitor cells, expanded in long-term neurosphere culture, promote functional recovery after focal ischemia in Mongolian gerbils

Transplantation of human neural stem cells (NSCs) is a promising potential therapy for neurologic dysfunctions after the hyperacute stage of stroke in humans, but large amounts of human NSCs must be expanded in long-term culture for such therapy. To determine their possible therapeutic potential for human stroke, human fetal neural stem/progenitor cells (NSPCs) (i.e., neurosphere-forming cells) were isolated originally from forebrain tissues of one human fetus, and expanded in long-term neurosphere culture (exceeding 24 weeks), then xenografted into the lesioned areas in the brains of Mongolian gerbils 4 days after focal ischemia. Sensorimotor and cognitive functions were evaluated during the 4 weeks after transplantation. The total infarction volume in the NSPC-grafted animals was significantly lower than that in controls. Approximately 8% of the grafted NSPCs survived, mainly in areas of selective neuronal death, and were costained with antibodies against neuronal nuclei antibody (NeuN), microtubule associated protein (MAP-2), glial fibrillary acidic protein (GFAP), and anti-2'3' cyclic nucleotide 3'-phosphodiesterase (CNPase). Synaptic structures between NSPCs-derived neurons and host neurons were observed. Furthermore, gradual improvement of neurologic functions was observed clearly in the NSPC-grafted animals, compared to that in controls. Human NSPCs, even from long-term culture, remarkably improved neurologic functions after focal ischemia in the Mongolian gerbil, and maintained their abilities to migrate around the infarction, differentiate into mature neurons, and form synapses with host neuronal circuits. These results indicate that in vitro-expanded human neurosphere cells are a potential source for transplantable material for treatment of stroke.     

Ganglioside complexes as new target antigens in Guillain-Barré syndrome

Antibodies specific for a complex of gangliosides GD1a and GD1b (GD1a/GD1b) were found in sera from eight of 100 patients with Guillain-Barre syndrome (GBS) by the use of enzyme-linked immunosorbent assay and thin-layer chromatogram immunostaining. Those sera also had antibody activities to such ganglioside complexes as GD1a/GM1, GD1b/GT1b, and GM1/GT1b but had little or no reactivity to the each isolated antigen. Clustered epitopes of the ganglioside complex in the plasma membrane may be targeted by such an antibody, and interaction between the antibody and ganglioside complex may induce the neuropathy.     

Heterogeneity and potentiation of AMPA type of glutamate receptors in rat cultured microglia

alpha-amino-hydroxy-5-methyl-isoxazole-4-propionate (AMPA) receptor in rat cultured microglia were analyzed precisely using flop- and flip-preferring allosteric modulators of AMPA receptors, 4-[2-(phenylsulfonylamino)ethylthio]-2,6-difluoro-phenoxyacetamide (PEPA) and cyclothiazide (CTZ), respectively. Glutamate (Glu)- or kainite (KA)-induced currents were completely inhibited by a specific blocker of AMPA receptor, LY300164, indicating that functional Glu-receptors in cultured microglia are mostly AMPA receptor but not KA receptor in many cells. Glu- and KA-induced currents were potentiated by PEPA and CTZ in a concentration-dependent manner. The ratio of the potentiation by PEPA to the potentiation by cyclothiazide varied with cells between 0.1 and 0.9, suggesting cell-to-cell heterogeneity of AMPA receptor subunits expressed in microglia. Quantitative RT-PCR revealed that GluR1-3 mainly occurred in the flip forms, which agreed with the stronger potentiation of receptor currents by CTZ vs. PEPA. Finally, the potentiation of microglial AMPA receptors by PEPA and CTZ inhibited the Glu-induced release of tumor necrosis factor-alpha (TNF-alpha) unpredictably. The increase in TNF-alpha release by Glu or KA required extracellular Na+ and Ca2+ ions but not mitogen-activated protein kinase (MAPK), suggesting the effects of PEPA and CTZ were not due to the inhibition of MAPK. These results suggest that potentiation of microglial AMPA receptors serves as a negative feedback mechanism for the regulation of TNF-alpha release and may contribute to the ameliorating effects of allosteric modulators of AMPA receptors.     

Delayed exacerbation of acute myocardial ischemia/reperfusion-induced arrhythmia by tracheal instillation of diesel exhaust particles

For understanding the relationship between the increased incidence of sudden cardiac death and air pollution, we examined the effects of intratracheal instillation of diesel exhaust particles (DEP) on acute myocardial ischemia/reperfusion-induced arrhythmia in rats. The animals received 1 mg DEP 24-48 h before the ischemia/reperfusion (DEP-pretreated group, DEP-PRE), and were subjected to 3 successive brief ischemia/reperfusion (3 min ischemia followed by 5 min reperfusion) procedures. These were to make the animals tolerant to ischemia/reperfusion-related myocardial deterioration. Thereafter the animals were subjected to a 10-min ischemia followed by a 30-min reperfusion. In the experiments, an increased mortality was observed in the DEP-PRE group compared to the vehicle (0.05% Tween 80-PBS)-treated group. Forty-six percent of the animals in DEP-PRE died during the first 3-min reperfusion period. The animals of other groups were intratracheally instilled with DEP at the beginning of ischemia/reperfusion experiment, or were pretreated with polyethylene glycol-conjugated superoxide dismutase (1000 IU kg(-1), iv). In these animals, incidences of both arrhythmia and mortality were similar to those in the animals treated with the vehicle. In experiments to investigate the effects of DEP on the biochemical and hematological parameters, neutrophil count was elevated by a higher dose (5 mg) of DEP at 24 h after the intratracheal instillation, and oxygen radical production, which was induced by 12-O-tetradecanoylphorbol 13-acetate, was enhanced at 72 h. These results indicate that intratracheal DEP instillation exacerbates short-period ischemia/reperfusion-induced arrhythmia. Delivery and activation of peripheral neutrophils and oxygen radicals produced in neutrophils might participate in this exacerbation. This is the first article that demonstrates the arrhythmogenicity of DEP using intratracheal instillation in rats.     

Comparison of the effects of latanoprost and timolol gel-forming solution on diurnal variation of intraocular pressure in normal-tension glaucoma

OBJECTIVE: To compare the effects of latanoprost (Lat) and timolol gel-forming solution (Tg) on the diurnal variation of intraocular pressure (IOP) in normal-tension glaucoma (NTG). SUBJECTS AND METHODS: A total of 47 NTG patients (47 eyes) were randomly assigned to receive Lat alone (25 eyes) or Tg alone (22 eyes). IOP was measured at fixed time points during 24 hours before and after treatment with each drug. In addition, blood pressure and pulse rate were measured before and after treatment. RESULTS: Lat reduced IOP significantly at all time points of measurement. Tg reduced IOP significantly at all time points of measurement except at 22:00 and 03:00. Percent reductions in the IOP at 03:00 and in the mean diurnal IOP were significantly greater in the Lat group than in the Tg group. In the Lat group there was no change in diastolic pressure or pulse rate after treatment, but in the Tg group these parameters decreased significantly. CONCLUSIONS: Comparison of diurnal variation of IOP before and after treatment shows that Lat is more effective than Tg in lowering IOP. In addition, Lat does not affect blood pressure or pulse rate.     

Neurocutaneous melanosis associated with malignant leptomeningeal melanoma in an adult: clinical significance of 5-S-cysteinyldopa in the cerebrospinal fluid---case report

A 35-year-old male presented with a variant of neurocutaneous melanosis with leptomeningeal malignant melanoma. He had three pigmented nevi from birth. He suffered diplopia followed by headache. T1-weighted magnetic resonance (MR) imaging revealed hydrocephalus and a small linear hyperintense lesion in the right frontal cortex. Several parts of the cortical sulci and the brain surface were slightly enhanced by gadolinium. Ventriculoperitoneal shunting was performed and extensive pigmented leptomeninges were recognized. Open biopsy established the diagnosis of leptomeningeal malignant melanoma. Combined chemoimmunotherapy was repeated every other month with monitoring of the 5-S-cysteinyldopa (5-S-CD) level in the cerebrospinal fluid (CSF). The 5-S-CD level decreased after each treatment, but the basal level steadily increased prior to the next treatment. Two years after the onset, he showed paraplegia caused by an extramedullary mass at the T-6 level. MR imaging showed that melanoma had involved the entire subarachnoid space including the whole spine. He underwent emergent removal of the spinal tumor and showed transient marked improvement. Further intensive chemotherapy was given. However, he died 31 months after the onset of massive proliferation of intracranial leptomeningeal melanoma. Measurement of CSF 5-S-CD levels is valuable for evaluating the therapeutic efficacy and for monitoring the progression of melanoma.