Cumulative incidence of femoral localized periosteal thickening (beaking) preceding atypical femoral fractures in patients with rheumatoid arthritis.

The incidence of localized periosteal thickening (LPT, also termed beaking) of the lateral cortex that often precedes an atypical femoral fracture (AFF) was not high in patients with rheumatoid arthritis (RA) but incomplete AFFs developed in two patients. Higher-dose prednisolone was a significant risk factor for LPT in patients with RA. INTRODUCTION: Atypical femoral fractures (AFFs) are stress fractures; bisphosphonate (BP) use is a major risk factor for the development of such fractures. Localized periosteal thickening (LPT, also termed beaking) of the lateral cortex often precedes a complete or incomplete AFF. We evaluated the incidence of latent LPT in patients with rheumatoid arthritis (RA), to evaluate LPT progression, and to define LPT risk factors. METHODS: A total of 254 patients with RA were included; all underwent annual X-ray evaluation, dual-energy X-ray absorptiometry, and analyses of serum and bone metabolic markers for 2-3 years. LPT of the lateral cortex was sought in femoral X-rays. RESULTS: The incidence of LPT was 2.4% (6/254). Among patients on both BP and prednisolone (PSL) at enrollment, the incidence was 2.3% (3/131). Two femurs of two patients with LPT developed incomplete AFFs; LPT was extensive and associated with endosteal thickening. One patient had been on BP and PSL and microscopic polyangiitis was comorbidity. The other was on a selective estrogen receptor modulator and PSL. A daily PSL dose >5 mg (OR 11.4; 95%CI 2.15-60.2; p = 0.004) and higher-dose methotrexate (OR 1.22; 95%CI 1.01-1.49; p = 0.043) were significant risk factors for LPT. CONCLUSIONS: The incidence of latent LPT was not high (2.4%) but incomplete AFFs developed in two RA patients. Higher-dose PSL because of a comorbid disease requiring glucocorticoid treatment other than RA or refractory RA were risk factors for LPT; X-ray screening for latent LPT would usefully prevent complete AFFs.

Characterization of patients with systemic lupus erythematosus who meet the diagnostic criteria for TAFRO syndrome.

Purpose TAFRO syndrome is a novel disorder manifesting as fever, anasarca, thrombocytopenia, renal insufficiency and organomegaly, and its etiology has not been clarified. The aim of this study was to elucidate similarities and differences between systemic lupus erythematosus (SLE) and TAFRO syndrome. Methods We examined 46 consecutive patients diagnosed with SLE and determined whether they meet the proposed diagnostic criteria for TAFRO syndrome (2015 version). Results Of the 46 patients with SLE, four (8.7%) also met the TAFRO syndrome criteria (TAFRO-like group). All patients in the TAFRO-like group were males, and their mean age was significantly higher than that of the non-TAFRO group (67.5 ± 8.7 vs. 39.3 ± 18.1 years, p = 0.004). C-reactive protein and γ-glutamyl transpeptidase levels were significantly higher, and frequencies of anti-dsDNA and anti-Sm antibodies were significantly lower in the TAFRO-like than non-TAFRO group. Elder cases (onset age ≥ 50 years) met significantly more categories of the diagnostic criteria for TAFRO syndrome than did those with younger cases. Conclusions Several patients with SLE, especially elder cases, showed features similar to those of TAFRO syndrome. Although exclusion of SLE is needed in the diagnostic criteria for TAFRO syndrome, TAFRO syndrome-like SLE should be considered.

High and pointed type of femoral localized reaction frequently extends to complete and incomplete atypical femoral fracture in patients with autoimmune diseases on long-term glucocorticoids and bisphosphonates.

Once a localized reaction (beaking) was detected, discontinuation of bisphosphonates (BPs) and switching to vitamin D supplementation or teriparatide therapy effectively improved its shape. When the localized reaction was high, of the pointed type, and/or accompanied by prodromal pain, the risks of complete and incomplete atypical femoral fracture increased and consideration of prophylactic fixation for such patients was required. INTRODUCTION: Femoral localized reaction (localized periosteal thickening of the lateral cortex, beaking) is reported to precede atypical femoral fractures (AFFs) and to develop in 8-10% of patients with autoimmune diseases taking BPs and glucocorticoids. The aims of the present study were to retrospectively investigate the shapes of localized reaction to consider how to manage the condition. METHODS: Twenty femora of 12 patients with autoimmune diseases who were on BPs and glucocorticoids exhibited femoral localized reaction. The heights of localized reaction were measured and the shapes classified as pointed, arched, and other. Localized reaction changes were divided into three categories: deterioration, no change, and improvement. A severe form of localized reaction was defined; this was associated with prodromal pain, de novo complete AFF, or incomplete AFF with a fracture line at the localized reaction. RESULTS: The mean height of localized reaction was 2.3 ± 0.8 mm (range, 1.0-3.7 mm) and the pointed type was 35%. Localized reaction was significantly higher (3.3 ± 0.8 vs. 2.1 ± 0.7 mm; p = 0.003) and the pointed type more common (78 vs. 27%; p = 0.035) in those with the severe form of localized reaction. Seven patients with localized reactions discontinued BPs just after localized reaction was detected, but five continued on BPs for 2 years. Localized reaction deterioration was more common in patients who continued than discontinued BPs (100 vs. 29%; p = 0.027). After 2 years, all patients had discontinued BPs and localized reaction did not deteriorate further in any patient. CONCLUSIONS: Once a localized reaction was detected, discontinuation of BPs and switching to vitamin D supplementation or teriparatide therapy effectively improved it. When the localized reaction was high, of the pointed type, and/or accompanied by prodromal pain, the risks of complete and incomplete AFF increased and consideration of prophylactic fixation for such patients was required.

The cumulative incidence of and risk factors for latent beaking in patients with autoimmune diseases taking long-term glucocorticoids and bisphosphonates.

SUMMARY: The incidence of beaking, which has been reported to precede atypical femoral fracture, was high and increased over 2 years in patients with autoimmune diseases who were taking bisphosphonates and glucocorticoids. Regular femoral X-rays are strongly recommended to screen for beaking, and bisphosphonate drug holidays should be considered. INTRODUCTION: Atypical femoral fractures (AFFs) have been recently recognized as complications associated with bisphosphonate (BP) use. AFFs are considered to be stress fractures; localized periosteal thickening of the lateral cortex is often present at the fracture site; this thickening is termed "beaking." Beaking has been reported to precede AFF. The aims of the present study were to evaluate the incidence of latent beaking in patients with autoimmune diseases taking BPs and glucocorticoids and to identify risk factors for beaking. METHODS: A total of 125 patients with autoimmune diseases who were taking BPs and glucocorticoids was included; 116 patients underwent X-rays and analysis of serum and urine bone metabolic markers annually for 2 years. Mean patient age was 54.5 years; there were 105 (90.5%) females and the mean duration of disease was 13.2 years. Focal lateral cortical thickening in femoral X-rays was defined as beaking. RESULTS: Beaking was detected in 15 femora of 10 patients (8.0%) at the time of recruitment. Over the 2-year observation period, the incidence of beaking increased to 21 femora of 12 patients (10.3%), and a complete AFF at the location of beaking occurred in one patient. Beaking was associated with a longer duration of BP treatment (6.1 ± 1.0 years vs. 5.0 ± 2.9 years, p = 0.01). Age 40-60 years, BP therapy ≥4 years, and diabetes mellitus were significantly associated with beaking. CONCLUSIONS: The incidence of beaking was high, and increased over 2 years, in patients with autoimmune diseases who were taking BPs and glucocorticoids. Regular femoral X-rays are strongly recommended to screen for beaking. Long-term BP/glucocorticoid use was a risk factor for beaking in patients with autoimmune diseases; BP drug holidays should be considered.

[Persistent hyperplastic primary vitreous--a case report of adult onset acute angle-closure glaucoma].

BACKGROUND: We report a patient with persistent hyperplastic primary vitreous(PHPV) who presented with acute angle-closure glaucoma in his adult life. CASE: A 30-year-old man had an attack of acute angle-closure glaucoma associated with retrolenticular fibrous tissue, atrophic retina, and elongated cilliary process in his right eye. RESULT: Ultrasound biomicroscopy(UBM) study showed iris bowing, shallow anterior chamber, and elongated cilliary body which were being pulled by the retrolenticular mass. The posterior chamber was normal. CONCLUSION: Although the mechanisms of secondary angle-closure glaucoma in PHPV are complicated, we suspected pupillary block resulting from constriction by the retrolenticular mass in this case.

[An ultrasound biomicroscopic study of eyes after non-penetrating trabeculectomy].

PURPOSES: We studied the control of intraocular pressure(IOP) by various types of blebs after non-penetrating trabeculectomy(NPT) and the difference between bleb formation after penetrating trabeculectomy(PT) and that after NPT. METHODS: The filtering blebs of 45 yeys from 40 patients after NPT were studied using ultrasound biomicroscopy. They were grouped into four types, and the space under the scleral flap was classified into three types. The filtering blebs and the space under the scleral flap were correlated with IOP level. RESULTS: Overall, 40% of the blebs were L(low-reflective) type, 16% H(high-reflective) type, 16% E (encapsulated) type, and 29% F(flattened) type, but in good IOP control cases 59% of the blebs were L type, 14% H type, 14% E type, and 14% F type. L type blebs were found in 94% of eyes with good IOP control. CONCLUSION: Though filtering blebs of the L type could produce sufficient IOP reduction, blebs after NPT showed a greater tendency to become flattened than after PT. Additional systematic therapy must be designed to maintain the L type of filtering blebs after NPT.

Measurement of microcirculation in optic nerve head by laser speckle flowgraphy in normal volunteers.

PURPOSE: To report blood flow in the optic nerve head between the right and left eyes or the superior and inferior neuroretinal rims in normal volunteers using laser speckle flowgraphy. METHODS: This prospective study included 120 eyes of 60 normal volunteers (mean age, 50.0 +/- 16.9 years; range, 21 to 77 years). The square blur rate was measured by laser speckle flowgraphy (Kyushu Institute of Technology, Iizuka, Japan). The sequence of eye measurements was randomized. In each eye, measurements were taken at the neuroretinal rim away from visible vessels. Linear regression analysis, paired two-tailed t test, and two-way analysis of variance were used for statistical analysis. P values less than.05 were accepted as statistically significant. RESULTS: There was a significant correlation in square blur rate between the right and left eyes (r = 0.587, P <.001). Square blur rate in the superior temporal neuroretinal rim significantly correlated with that in the inferior temporal neuroretinal rim in each of the right (r = 0.546, P <.001) and left (r = 0.465, P <.001) eyes. Square blur rate in the right eye was higher than that in the left eye (P =.049). Square blur rate in the superior neuroretinal rim was higher than that in the inferior neuroretinal rim in both the right (P =.035) and left (P =. 005) eyes. CONCLUSION: There were statistically significant differences of optic nerve head blood flow in normal volunteers using laser speckle flowgraphy between the right and left eyes and between the superior and inferior temporal neuroretinal rims. These normal data can be used for understanding physiological ocular hemodynamics.

Measurement of microcirculation in the optic nerve head by laser speckle flowgraphy and scanning laser Doppler flowmetry.

PURPOSE: To evaluate and compare blood flow measurements by laser speckle flowgraphy and scanning laser Doppler flowmetry in the optic nerve head of normal volunteers. METHODS: This prospective study included 60 eyes of 60 normal volunteers (50.0 years; range, 21 to 77 years). Measurements were taken at the temporal neuroretinal rim away from visible vessels. The square blur rate, a quantitative index of relative blood velocity, was measured by laser speckle flowgraphy. Using scanning laser Doppler flowmetry, volume, flow, and velocity were measured at the same neuroretinal rim locations. RESULTS: The average square blur rate, volume, flow, and velocity were 7.11 +/- 1.65, 7.74 +/- 3.19, 151.85 +/- 70.63, and 0.53 +/- 0. 23 arbitrary units, respectively (n = 60). Square blur rate correlated significantly with flow and velocity (r =.361, P =.005; r =.359, P =.005, respectively). However, there was no significant correlation between square blur rate and volume (r =.101, P =.441). Although square blur rate decreased significantly with increasing age (r = -.375, P =.003), volume, flow, or velocity showed no significant correlation with age (r = -.249, P =.054; r = -.166, P =. 205; r = -.143, P =.275, respectively). Square blur rate also decreased significantly with mean blood pressure (r = -.315, P =. 014), but volume, flow, or velocity showed no significant correlation with mean blood pressure (r = -.159, P =.225; r = -.059, P =.654; r = -.043, P =.742, respectively). CONCLUSION: We found only a weak correlation between the blood flow indexes, as measured by laser speckle flowgraphy and scanning laser Doppler flowmetry because of basic differences in the principles of measurement.

Acute infection of Sindbis virus induces phosphorylation and intracellular translocation of small heat shock protein HSP27 and activation of p38 MAP kinase signaling pathway.

In general, viral infection is supposed to induce stress responses in the host cell. However, very few detailed observations about virus-induced stress responses have been reported. Here we investigated specific stress responses in Vero cells infected with Sindbis virus (SV), a single-stranded RNA virus, acute infection with which is known to cause apoptotic cell death in the host cells. Prior to the onset of apoptosis, p38 mitogen-activated protein kinase (MAPK) and c-Jun NH2-terminal kinases (JNKs) were activated. Subsequently, a 27-kDa heat shock protein (HSP27) became phosphorylated, and intracellular distribution of HSP27 was changed from the cytoplasm to the perinuclear region. These results indicate that the cellular signaling cascades activated by pro-inflammatory cytokines and environmental stresses are also activated as a result of lytic infection with SV. These responses may contribute to the delayed onset of apoptosis in the host cells and the facilitation of viral replication.

Constant hue loci of unique and binary balanced hues at 10, 100, and 1000 Td.

Constant hue loci for unique red, yellow, green, and blue and the loci of four binary balanced hues (e.g., equally reddish and yellowish) were measured at 10, 100, and 1000 Td for two observers. Wavelengths of the unique hues were not invariant from 10 to 1000 Td. In Judd's modification of the 1931 CIE chromaticity diagram, only the unique yellow loci at 10 and 1000 Td plotted as straight lines. The other constant hue loci were curved, and all the constant hue loci changed with retinal illuminance.

Additivity of red chromatic valence.

The additivity of red chromatic valence was investigated by the hue cancellation method for 4 normal observers. Additivity held for wavelength combinations of 610-680 nm and 400-440 nm. When using 400-680 nm, additivity failure of enhancement type was found for two observers, reduction type failure for a third, and additivity, for a forth. The results suggest a nonlinear property of the red-green process for some observers and are discussed in terms of the contribution of B-cones to the process.