Etiology of acute ischaemic cerebrovascular disease associated with rheumatoid arthritis: changes with progression of anti-inflammatory therapy.

BACKGROUND AND PURPOSE: In patients with rheumatoid arthritis (RA), the serum C-reactive protein (CRP) level is associated with ischaemic cerebrovascular disease (iCVD). Acute iCVD patients with RA were investigated, assessing changes of clinical characteristics and CRP with progress in RA treatment. METHODS: Patients hospitalized for acute iCVD from August 2002 to February 2018 were divided into two groups at February 2010. Patients with RA were retrospectively identified. The incidence of RA, the occurrence of acute exacerbation of inflammation due to causes other than synovitis preceding iCVD (non-synovitis AEI) and serum CRP were compared. RESULTS: In the first and second periods, 23/1203 patients (1.9%) and 22/1094 patients (2.0%) respectively had acute iCVD with RA. Non-synovitis AEI was significantly less frequent in the second period (5%, n = 1) than in the first period (35%, n = 8) (P < 0.05). CRP was significantly lower at iCVD onset in the second period [median and interquartile range 2.72 (0.89-4.5) mg/dl vs. 0.34 (0.12-1.19) mg/dl, P < 0.01]. Excluding nine patients with non-synovitis AEI, CRP was still lower in the second period [1.21 (0.47-2.72) mg/dl vs. 0.33 (0.11-0.98) mg/dl, P < 0.01]. CRP levels before both iCVD and non-synovitis AEI tended to be lower in the second period [1.53 (0.3-2.78) mg/dl vs. 0.69 (0.06-1.28) mg/dl, P = 0.059]. Two patients using tocilizumab developed iCVD despite persistently low CRP levels. CONCLUSIONS: With progress in treatment, RA-related inflammation was better suppressed and CRP decreased, but the prevalence of RA amongst acute iCVD patients was unchanged. Strategies for tighter control of inflammation are needed, and a new biomarker may be required in patients using tocilizumab.

Effects of switching weekly alendronate or risedronate to monthly minodronate in patients with rheumatoid arthritis: a 12-month prospective study.

UNLABELLED: Switching weekly ALN or RIS to monthly MIN in patients with RA, of whom two-thirds were treated with low-dose PSL, significantly decreased bone turnover markers and increased BMD at 12 months, suggesting that monthly MIN may be an effective alternative treatment option of oral bisphosphonate treatment. INTRODUCTION: The aim of this prospective, observational study was to evaluate the effects of switching weekly alendronate (ALN 35 mg) or risedronate (RIS 17.5 mg) to monthly minodronate (MIN 50 mg) in patients with rheumatoid arthritis (RA). METHODS: Patient characteristics were as follows: n = 172; 155 postmenopausal women, age 65.5 (44­87) years; T-score of lumbar spine (LS), −1.4; total hip (TH), −1.8; femoral neck (FN), −2.1; dose and rate of oral prednisolone (2.3 mg/day), 69.1 %; prior duration of ALN or RIS, 46.6 months; were allocated, based on their preference, to either the (1) continue group (n = 88), (2) switch-from-ALN group (n = 44), or (3) switch-from-RIS group (n = 40). RESULTS: After 12 months, increase in BMD was significantly greater in group 3 compared to group 1: LS (4.1 vs 1.2 %; P < 0.001), TH (1.9 vs −0.7 %; P < 0.01), and FN (2.7 vs −0.5 %; P < 0.05); and in group 2 compared to group 1: LS (3.2 vs 1.2 %; P < 0.05) and TH (1.5 vs −0.7 %; P < 0.01). The decrease in bone turnover markers was significantly greater in group 3 compared to group 1: TRACP-5b (−37.3 vs 2.5 %; P < 0.001), PINP (−24.7 vs −6.2 %; P < 0.05), and ucOC (−39.2 vs 13.0 %; P < 0.05); and in group 2 compared to group 1: TRACP-5b (−12.5 vs 2.5 %; P < 0.05) at 12 months. CONCLUSIONS: Switching weekly ALN or RIS to monthly MIN in patients with RA may be an effective alternative treatment option of oral bisphosphonate treatment.

Eight-year preservation of knee function with radiographic healing phenomena after anti-tumor necrosis factor-α therapy for a severely erosive knee in a young patient with rheumatoid arthritis.

A 23-year-old woman developed rheumatoid arthritis (RA). The pain in her right knee was aggravated and anti-tumor necrosis factor (TNF)-α therapy was selected at the age of 35. The range of motion and Larsen grade were 5º to 120º and 4, respectively. Infliximab and etanercept therapies were quite effective and the pain of the right knee improved. An X-ray at 1 year showed radiographic healing phenomena that included reappearance of a clear visible cortical plane, partial filling-in of erosions and cysts, and sclerosis of the subchondral bone. An X-ray at the age of 43 showed that the radiographic healing phenomena were still preserved after 7 years. The right knee remained pain-free although the Larsen grade was still 4, and the knee function was preserved for 8 years. In conclusion, anti-TNF-α therapy may preserve knee function with radiographic healing phenomena and prevent total arthroplasty of severely erosive knees in young RA patients.

Rapid method for monitoring galactosylation levels during recombinant antibody production by electrospray mass spectrometry with selective-ion monitoring.

This report describes a simple and rapid method to determine the relative amounts of glycoforms differing in terminal galactose on a recombinant antibody produced in Chinese hamster ovary (CHO) cells. The method uses a single quadrupole mass spectrometer coupled to an HPLC system to quantify the glycoform amounts found on a recombinant antibody that binds to the human CD20 antigen. Samples from the recombinant antibody process are reduced and injected directly into the HPLC system where the heavy and light chain antibody fragments, as well as host-cell protein contaminants, are separated chromatographically. Mass-selective detection is performed in the selected-ion monitoring (SIM) mode to monitor the most abundant (38+) ions corresponding to the glycoforms found on the heavy chain of the recombinant antibody. Results obtained using the assay demonstrate good sensitivity, linearity and reproducibility. Comparison to a method using capillary electrophoresis (CE) of the labeled free oligosaccharides demonstrates similar quantitation of the glycoforms in the recombinant antibody. The LC-MS method provides a simple and rapid means for accurately quantifying antibody glycoforms directly from cell culture and other process samples.

Intramedullary nailing of unstable diaphyseal fractures of the tibia with distal intraarticular involvement.

OBJECTIVE: To evaluate the efficacy of intramedullary nailing in diaphyseal tibia fractures with distal intraarticular involvement. DESIGN: Retrospective. SETTING: Henry Ford Hospital, a level I trauma center. PATIENTS/PARTICIPANTS: Twenty patients with twenty fractures at an average of twenty-two months of follow-up were evaluated. There were fifteen closed and five open fractures. INTERVENTION: All fractures were stabilized with lag screw fixation (with or without supplemental plates) of the intraarticular-fracture extension or ankle fracture, and intramedullary nailing of the diaphyseal tibia fracture. MAIN OUTCOME MEASUREMENTS: Time to bony union, malunion, knee and ankle range of motion, early arthrosis, and any complications of treatment were assessed. RESULTS: Nineteen fractures healed, with an average time to bony union of seventeen weeks. One nonunion after a grade IIIB open fracture required exchange nailing and healed after sixty-two weeks. Nineteen fractures had excellent alignment after healing. There were no infections. CONCLUSIONS: The indications for intramedullary nailing of unstable diaphyseal tibia fractures may be extended to include certain fractures with distal extension into the ankle joint, as well in a tibial shaft fracture occurring in combination with a noncontiguous ipsilateral ankle fracture.

Pressure effects on the composition and thermal behavior of lipids from the deep-sea thermophile Methanococcus jannaschii.

The deep-sea archaeon Methanococcus jannaschii was grown at 86 degrees C and under 8, 250, and 500 atm (1 atm = 101.29 kPa) of hyperbaric pressure in a high-pressure, high-temperature bioreactor. The core lipid composition of cultures grown at 250 or 500 atm, as analyzed by supercritical fluid chromatography, exhibited an increased proportion of macrocyclic archaeol and corresponding reductions in aracheol and caldarchaeol compared with the 8-atm cultures. Thermal analysis of a model core-lipid system (23% archaeol, 37% macrocyclic archaeol, and 40% caldarchaeol) using differential scanning calorimetry revealed no well-defined phase transition in the temperature range of 20 to 120 degrees C. Complementary studies of spin-labeled samples under 10 and 500 atm in a special high-pressure, high-temperature electron paramagnetic resonance spectroscopy cell supported the differential scanning calorimetry phase transition data and established that pressure has a lipid-ordering effect over the full range of M. jannaschii's growth temperatures. Specifically, pressure shifted the temperature dependence of lipid fluidity by ca. 10 degrees C/500 atm.

Scaphoid fracture displacement with forearm rotation in a short-arm thumb spica cast.

Three-dimensional motion between the fragments of an experimental scaphoid waist fracture was measured during dynamic forearm pronation and supination in a short-arm thumb spica cast with and without applied tendon loads. Metal markers placed in each fragment were tracked using high-speed biplane radiographic image sequences and stereophotogrammetric analysis. Peak displacements (from the intact state) exceeded 1 mm in all specimens, with the largest movements occurring in the radial direction during pronation (mean: 2.1 mm unloaded, 2.5 mm loaded). Total range of displacement motion between fragments exceeded 3 mm (mean ulnar/radial direction: 3.4 mm unloaded, 4.1 mm loaded). Dorsal/palmar and proximal/distal displacements were minimal except at the extremes of forearm pronation/supination. Rotations between fragments were small (within +/- 6 degrees) and varied considerably across specimens. No significant differences were found between loaded and unloaded trials. Thus, in the absence of long-arm thumb spica casting to limit forearm rotation, significant motion between the fragments of a scaphoid waist fracture is likely.

Effective treatment of the postoperative maxillary cyst by marsupialization.

The postoperative maxillary cyst occurs as a delayed complication after radical surgical intervention in the maxillary sinus. The recommended procedures for treating this entity have been enucleation followed by formation of an antronasal window, primary closure, or open packing. To prevent recurrence and unnecessary tissue destruction from surgery, marsupialization was performed in eight unilocular postoperative maxillary cysts. With the exception of a case in which the long-term results could not be obtained, the cysts disappeared in four months to two and a half years. Possible indications for marsupialization of the postoperative maxillary cyst are discussed.

Continuous culture of Methanococcus jannaschii, an extremely thermophilic methanogen.

Methanococcus jannaschii, an extremely thermophilic methanogen isolated from a deep-sea hydrothermal vent, was grown at 80 degrees C in continuous culture on a mineral salts medium gassed with H(2) and CO(2) at three different flow rates. The maximum specific growth rate was 0.56 h(-1), and the maximum specific methane productivity was 0.32 (mol g(-1) h(-1)). Uncoupling of growth and methane production was evidenced by an increase in teh non-growth-associated rate of methane formation, beta, with increasing gaseous input. The specific hydrogenase activity exhibited growth-assiciated behaviour at low growth rates, but showed no dependence on growth at higher growth rates. The growth dependence of hydrogenase activity is consistent with the pressure dependence of hydrogenase activity measured in previous experiments. In contrast, the specific protease activity was independent of the growth rate over the entire range of dilution rates studied. (c) 1994 John Wiley & Sons, Inc.

The postoperative maxillary cyst: report of 71 cases.

The postoperative maxillary cyst develops as a delayed complication many years after surgical intervention in the maxillary sinus. The clinical, radiographic, surgical, and histologic findings of 71 such cysts are described. The cysts occurred most frequently ten to 30 years after radical operations. The most common symptoms were swelling or pain of the cheek and the mucogingival fold of the maxilla. Radiographically, the lesions were either unilocular or multilocular, and bony perforation was noticed in half of them. The cysts were treated surgically in all cases. Most of them had a thin wall, lined with ciliated columnar epithelium. The results of our analysis and possible pathogenesis are discussed.

Negative dromotropic effect of diazepam on the AV node of dog heart in situ.

Effect of diazepam on the AV nodal conductivity was studied using a direct perfusion technique of the canine AV node artery in situ. As compared to acetylcholine which induced a rapid onset of third degree AV block with prompt recovery, diazepam injected into the AV node artery in doses from 300 micrograms to 3 mg elicited first to third degree AV blocks of longer duration following gradual prolongation of PR interval. The response was not affected by bilateral vagotomy and sympathectomy. Pretreatment of the AV node with hexamethonium or atropine also failed to modify the diazepam-induced AV blocks. Thus, diazepam seemed to suppress conductivity of the AV node by a direct action. The AV nodal tachycardia induced by infusion of norepinephrine was readily antagonized by a single injection of diazepam, but norepinephrine failed to reverse the AV block induced by diazepam infusion.

Biphasic response of the SA node of the dog heart in vivo to selective administration of ketamine.

Effect of ketamine on the SA node of the dog heart was studied in vivo using a selective perfusion technique of the SA node artery. Injections of ketamine in doses from 100 microgram to 3 mg into the artery produced a depression of the SA nodal activity by a direct action. This depression was followed by the sudden appearance of a stimulatory phase. Bilateral vagotomy and sympathectomy or prior administration of a ganglion blocker failed to inhibit the occurrence of the ketamine-induced tachycardia, while it was completely abolished in the reserpinized dogs or by a prior injection of a beta-blocking agent into the SA node artery. This may indicate that an activation of the peripheral adrenergic mechanism plays an important role in the induction of the excitatory effect of ketamine injected in the SA node artery.

A seroepidemiologic survey of human T-cell lymphotropic virus type I in two Hawaiian hematologic-oncologic practices.

A seroepidemiologic survey for antibodies to the human T-cell lymphotropic virus type I (HTLV-I) was carried out in two Hawaiian hematologic-oncologic practices. Specimens of serum or plasma from 215 donors were assayed using the ELISA technique, followed by the Western blot technique to confirm antibody specificity to HTLV-I. Of 214 seropositive donors, 16 (7.5%) were positive. Of 172 donors of Japanese ancestry, 16 (9.3%) were seropositive; none were white, Chinese, Filipino, or Pacific Islander. One donor contracted the virus through blood transfusions. The results suggest that HTLV-I was introduced to Hawaii with the Japanese immigration.