Hypertrophic Pachymeningitis with Characteristics of Both IgG4-related Disorders and Granulomatosis with Polyangiitis.

We herein report a 73-year-old man with isolated hypertrophic pachymeningitis (HP) showing serological and pathological characteristics of both IgG4-related disorders and granulomatosis with polyangiitis. The patient presented with chronic onset headaches and ophthalmalgia. Brain magnetic resonance imaging (MRI) revealed a hypertrophic enhanced dura mater. Serum IgG4 and myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA) levels were elevated. A dura mater biopsy showed infiltration of numerous IgG4-positive plasma cells and granulomatous inflammation without apparent vasculitic lesions, storiform fibrosis, or obstructive phlebitis. Corticosteroid treatments improved his clinical symptoms and MRI findings. There have been reports of MPO-ANCA-positive IgG4-related HP presenting as granulomatous inflammation in the dura mater.

Radial linear perivascular emphasis in coronavirus disease 2019-associated acute disseminated encephalomyelitis.

A 62-year-old woman with coronavirus disease (COVID-19) developed coma on day 19 after her pneumonia was ameliorated. Brain magnetic resonance imaging with gadolinium showed radial linear perivascular enhancement, typically seen in glial fibrillary acidic protein (GFAP) astrocytopathy, although anti-GFAP antibody results were negative. Her consciousness recovered with high-dose steroid administration. We diagnosed the patient with COVID-19-associated acute disseminated encephalomyelopathy (ADEM) with radial linear perivascular emphasis.

Myo-inositol treatment increases serum plasmalogens and decreases small dense LDL, particularly in hyperlipidemic subjects with metabolic syndrome.

BACKGROUND AND AIM: We have previously shown that serum plasmalogen levels positively correlate with HDL, and significantly decrease with aging, and may be related to LDL particle size. The objective of the present study was to investigate the effects of increased serum plasmalogens on lipidosis, particularly the appearance of atherogenic small dense LDL (sdLDL), of subjects with hyperlipidemia and metabolic syndrome (MetS). METHODS AND RESULTS: The effects of increased serum plasmalogen levels, induced by 2 wk of myo-inositol treatment, on several clinical and biochemical parameters were examined in 17 hyperlipidemic subjects including some with MetS. After myo-inositol treatment, significant increases in plasmalogen-related parameters, particularly ChoPlas, and significant decreases in atherogenic cholesterols including sdLDL, were observed. Among the hyperlipidemic subjects treated with myo-inositol, compared to subjects without MetS, subjects with MetS had a significant increase in plasmalogens and a tendency towards reduced sdLDL, high sensitivity C-reactive protein (hsCRP), and blood glucose levels. Correlation analyses between the measured parameters showed that plasmalogens, as well as HDL, function as beneficial factors, and that sdLDL is a very important risk factor that shows positive correlations with many other risk factors. CONCLUSION: These results suggest that increased plasmalogen biosynthesis and/or serum levels are especially effective in improving MetS among hyperlipidemic subjects with MetS.

The sensorimotor transformation of cross-modal spatial information in the anterior intraparietal sulcus as revealed by functional MRI.

The parietal cortex in monkeys and humans has been shown to play an important role in the transformation of sensory information to motor commands. However, it is still unclear whether in humans, these areas are divided functionally into subregions based on different combinations of sensory and motor modalities. To identify subregions in the parietal cortex involved in the sensorimotor information transformation between different modalities, functional MRI was used to examine brain areas activated during tasks requiring different sensorimotor transformations--i.e., various combinations of eye (saccade) or finger movements triggered by visual or somatosensory cues. We then compared the activations between cross-modal conditions (eye movements triggered by somatosensory cues and finger movements triggered by visual cues) and intramodal (eye movements triggered by visual cues and finger movements triggered by somatosensory cues) conditions. Although the parietal cortex was involved in all tasks regardless of sensorimotor combinations, the only region activated to a greater degree in the cross-modal conditions compared to the intramodal conditions was the anterior portion of the intraparietal sulcus (a-IPS). The results suggest that the a-IPS plays an important role in the sensorimotor transformation of cross-modal spatial information.

Axial correction of pes varus by transverse-opening wedge osteotomy and T-plate fixation with beta-tricalcium phosphate (beta-TCP) transplantation in dachshunds.

Axial correction was performed surgically in two miniature dachshunds presenting with lateral patellar dislocation and limping caused by pes varus. Pes varus had resulted from asymmetric closure of the physis of the distal tibia. Prior to surgery, osteotomy was simulated by measuring X-ray films to determine the distance required for the wedge opening. Transverse-opening wedge osteotomy was performed on the medial side of the distal tibia, and beta-tricalcium phosphate (beta-TCP) was inserted in a wedge shape into the area created by the cuneiform osteotomy. Finally, the tibia was fixed by a veterinary 1.5/2.0-mm T-plate. Both dogs were able to walk a few days after surgery, and the lateral dislocation of the patella normalized almost completely in about one month. At two months, X-ray films showed that the implant had remained in position without any dislocation, and the beta-TCP had fused with the surrounding bone.

[Successful balloon-occluded retrograde transvenous obliteration (B-RTO) in a case of symptomatic epilepsy with hepatic encephalopathy due to non-cirrhotic porto-systemic shunt].

We report a 66-year-old man with hepatic encephalopathy due to a non-cirrhotic porto-systemic shunt during the course of treatment for epilepsy with sodium valproate. The patient developed symptomatic epilepsy after an operation for intracranial arterio-venous malformation at the age of 41, and had been treated with sodium valproate and phenytoin since. At the age of 66, he developed convulsions that were thought to be symptomatic epilepsy with hyperammonemia. Despite sodium valproate having been tapered rapidly and then discontinued, hyperammonemia continued. Abdominal contrast enhanced CT demonstrated a large spleno-renal shunt. Although he was treated with lactulose, he developed encephalopathy with hyperammonemia several times. At the age of 67, we occluded the spleno-renal shunt by balloon-occluded retrograde transvenous obliteration (B-RTO), after which, his clinical symptoms improved, together with normalizing of the ammonia level and EEGs.

[Significance of the stool occult blood test in patients with thrombotic disease under treatment with low dose aspirin].

We encountered lower gastrointestinal bleeding in 16 patients taking a low dose of aspirin and examined the effect of low aspirin dose on the stool occult blood test in 49 thrombotic patients (mean: 76.7 +/- 9.6 years old) including 39 with cerebral infarction, 8 with ischemic heart disease and 2 with atrial fibrillation. The mean aspirin dosage was 81 mg/day over a period of 6-288 weeks (mean: 86.4 +/- 66.9 weeks). Positive occult blood test was seen in 16/49 (32.7%). Severe lower gastrointestinal bleeding was observed in one case (2%) with colon diverticulosis. Aspirin dosage per patient was significantly higher (p<0.01) in the occult blood test positive group (60.1 +/- 47.2 g) than in the occult blood test negative group (42.6 +/- 32.8 g). The positive ratio of occult blood test was significantly higher (p<0.01) in the aspirin and antithrombotic drugs-taking group (8/5; positive/negative) than in the aspirin-taking group (8/28; p/n), whereas it was not significant between the aspirin taking-group and aspirin not taking-group. The odds ratio between aspirin and antithrombotic drugs (warfarin, beraprost, cilostazol or ticlopidine)-taking group and the aspirin-taking group was 3.47 (p<0.05). A low dose of aspirin was associated with a positive occult blood test. Aspirin should be carefully administered when patient has a diverticle or is taking other antithrombotic drugs.

In vitro microbiological characterization of a novel azalide, two triamilides and an azalide ketal against bovine and porcine respiratory pathogens.

Several novel 15-membered-ring macrolide agents (azalide 1, triamilides 2 and 3, and the azalide 3,6-ketal 4) were identified as potential antibacterial agents against Mannheimia (formerly named as Pasteurella) haemolytica, Pasteurella multocida, Haemophilus somnus and Actinobacillus pleuropneumoniae, important etiological agents of bovine and porcine respiratory disease. Compound 3 is the major component of the antibiotic tulathromycin. Antibacterial activity against tilmicosin-resistant P. multocida field isolates was also tested. In vitro MIC 50/90 analysis revealed that the four newly synthesized compounds were more potent than tilmicosin against M. haemolytica (4 to approximately 8x), P. multocida (8 to approximately 16x), A. pleuropneumoniae (4x), H. somnus (2x and 16x), and tilmicosin-resistant P. multocida (32x). In time-kill kinetic studies, all four novel compounds and tilmicosin showed bactericidal activity against M. haemolytica, P. multocida and A. pleuropneumoniae at both 4x and 8x MIC. A functional assay using genetically defined mutants revealed that all four novel compounds were poorer substrates for the efflux pump, AcrA/B system, than tilmicosin. A pH study using LPS mutants indicated that the enhanced in vitro potency of the triamilides, particularly compound 3 was mainly due to better penetration of the molecule through the outer membrane. The third amine group at the C-4'' position of the triamilde molecules contributed to this increased membrane penetration by increasing overall basicity. These studies indicate that the four novel compounds have potential as antibacterial agents against bovine and porcine respiratory disease.

Significance of plasma D-dimer in relation to the severity of atherosclerosis among patients evaluated by non-invasive indices of cardio-ankle vascular index and carotid intima-media thickness.

The aim of this study is to elucidate the usefulness of plasma D-dimer for the prediction of thrombotic events in highly atherosclerotic patients. The severity of atherosclerosis was measured by non-invasive methods including cardio-ankle vascular index (CAVI) and carotid intima-media thickness (IMT) in 100 patients with atherosclerosis aged 72.1 years on average. CAVI was significantly correlated with the levels of D-dimer, platelet aggregation (Plt Aggre), uric acid (UA), creatinine (Cr), blood urea nitrogen (BUN), and C-reactive protein (CRP), whereas IMT was significantly correlated with the levels of Cr, BUN, and CRP. CAVI and IMT were suitable for stratification of the patients. A comparison of hemostatic markers (D-dimer, fibrinogen and Plt Aggre) between the less sclerotic group (group A; CAVI <8.0 and IMT <1.1 mm, n = 26) and the highly sclerotic group (group B; CAVI >8.0 and IMT >1.1 mm, n = 32) revealed that the incidence of thrombosis was significantly higher in group B (18.8%) than in group A (3.8%) and that D-dimer was significantly higher (p < 0.01, Mann-Whitney U test) in group B (0.48 mug/ml, median) than in group A (0.32 mug/ml, median). Moreover, multiple linear regression analyses of CAVI and IMT indicated that D-dimer and age were significant variables. In conclusion, D-dimer is significantly associated with thrombosis in highly atherosclerotic patients.

Liver sarcoidosis that presented with dysphagia.

We report a case of liver sarcoidosis with dysphagia. Although akinesia of the soft palate, disappearance of the palatal reflex, and pyramidal signs indicated brainstem lesions, brain magnetic resonance imaging showed no lesion and the focus was obscure. Iritis, parotiditis, and hilar lymphadenopathy supported the diagnosis of sarcoidosis. However, lung biopsy was normal. Finally, sarcoidosis was diagnosed by liver biopsy. We speculated that microgranulomas in the brainstem that did not exhibit imaging abnormalities causing the neurological symptoms and that liver biopsy can be an effective diagnostic tool even for cases that presented with neurological signs, but no gastrointestinal symptom.

Circulatory basis of fMRI signals: relationship between changes in the hemodynamic parameters and BOLD signal intensity.

Blood oxygenation level-dependent functional magnetic resonance imaging (BOLD-fMRI) is widely used as a tool for functional brain mapping. During brain activation, increases in the regional blood flow lead to an increase in blood oxygenation and a decrease in paramagnetic deoxygenated hemoglobin (deoxy-Hb), causing an increase in the MR signal intensity at the site of brain activation. However, not a few studies using fMRI have failed to detect activation of areas that ought to have been activated. We assigned BOLD-positive (an increase in the signal intensity), BOLD-negative (a decrease in the signal intensity), and BOLD-silent (no change) brain activation to respective circulatory conditions through a description of fMRI signals as a function of the concentration of oxygenated Hb (oxy-Hb) and deoxy-Hb obtained with near-infrared optical imaging (NIOI). Using this model, we explain the sensory motor paradox in terms of BOLD-positive, BOLD-negative, and BOLD-silent brain activation.

Synthesis, stereochemical assignment and biological activity of a novel series of C-4" modified aza-macrolides.

Modification of the cladinose C-4" position via manipulation of the corresponding keto derivatives afforded two stereochemically pure series of compounds. The synthesis and structure determination of these compounds is described within. The in vitro and in vivo biological activity of this novel series of C-4" modified macrolides is also described.

Azalide 3,6-ketals: antibacterial activity and structure-activity relationships of aryl and hetero aryl substituted analogues.

Aryl and hetero aryl substituted 3,6-ketals of 15-membered azalide analogues were synthesized and were found to have potent in vitro antibacterial activity against veterinary pathogens, including Staphylococcus aureus and Pasteurella multocida.

Synthesis and activity of a novel class of tribasic macrocyclic antibiotics: the triamilides.

The stereoselective synthesis of two novel series of tribasic macrocyclic antibiotics with potent in vitro activity against Pasteurella multocida and Escherichia coli strains of bacteria is described. The in vitro activity can be significantly influenced by the nature of the substituents on the C-4" aminoalcohol, with the stereochemistry of the C-4" alcohol playing a less critical role. The effect of substitution and stereochemistry on the in vivo activity in a murine model of respiratory infection is also described.

Synthesis and SAR of azalide 3,6-ketal aromatic derivatives as potent Gram-positive and Gram-negative antibacterial agents.

3,6-Ketals of 15-membered azalide pseudoaglycones are a novel series of macrolide antibiotics. The aromatic derivatives of the azalide 3,6-ketals demonstrated potent antibacterial activities against both Gram-positive and Gram-negative bacteria.