Aberrant MHC class II expression in mouse joints leads to arthritis with extraarticular manifestations similar to rheumatoid arthritis

Genetic susceptibility to rheumatoid arthritis (RA) is associated with certain MHC class II molecules. To clarify the role of these determinants in RA, we generated the D1CC transgenic mouse that expressed genes involved in antigen processing and presentation by the MHC class II pathway in joints. The class II transactivator, which was transcribed from the rat collagen type II promoter and enhancer, directed the expression of these genes. In D1CC mice congenic for the H-2(q) (DBA/1) background, small amounts of bovine collagen type II in adjuvant induced reproducibly an inflammatory arthritis resembling RA. Importantly, these stimuli had no effect in DBA/1 mice. Eighty-nine percent of D1CC mice developed chronic disease with joint swelling, redness, and heat in association with synovial proliferation as well as pannus formation and mononuclear infiltration of synovial membranes. Granulomatous lesions resembling rheumatoid nodules and interstitial pneumonitis also were observed. As in patients with RA, anticyclic citrullinated peptide antibodies were detected during the inflammatory stage. Finally, joints in D1CC mice displayed juxtaarticular demineralization, severe joint space narrowing, and erosions, which led to ankylosis, but without the appearance of osteophytes. Thus, aberrant expression of MHC class II in joints facilitates the development of severe erosive inflammatory polyarthritis, which is very similar to RA.     

Health-related quality of life measurement in patients with chronic respiratory failure

The improvement of health-related quality of life (HRQL) is an important goal in managing patients with chronic respiratory failure (CRF) receiving long-term oxygen therapy (LTOT) and/or domiciliary noninvasive ventilation (NIV). Two condition-specific HRQL questionnaires have been developed to specifically assess these patients: the Maugeri Respiratory Failure Questionnaire (MRF) and the Severe Respiratory Insufficiency Questionnaire (SRI). The MRF is more advantageous in its ease of completion; conversely, the SRI measures diversified health impairments more multi-dimensionally and discriminatively with greater balance, especially in patients receiving NIV. The SRI is available in many different languages as a result of back-translation and validation processes, and is widely validated for various disorders such as chronic obstructive pulmonary disease, restrictive thoracic disorders, neuromuscular disorders, and obesity hypoventilation syndrome, among others. Dyspnea and psychological status were the main determinants for both questionnaires, while the MRF tended to place more emphasis on activity limitations than SRI. In comparison to existing generic questionnaires such as the Medical Outcomes Study 36-item short form (SF-36) and disease-specific questionnaires such as the St. George's Respiratory Questionnaire (SGRQ) and the Chronic Respiratory Disease Questionnaire (CRQ), both the MRF and the SRI have been shown to be valid and reliable, and have better discriminatory, evaluative, and predictive features than other questionnaires. Thus, in assessing the HRQL of patients with CRF using LTOT and/or NIV, we might consider avoiding the use of the SF-36 or even the SGRQ or CRQ alone and consider using the CRF-specific SRI and MRF in addition to existing generic and/or disease-specific questionnaires.     

Impairment in toileting behavior after a stroke

Aim

Dependence for toileting is the most problematic aspect for patients after a stroke. However, the relative difficulty of each component of toileting and the predictors for independent performance of these activities are unknown. We investigated these issues in stroke patients using Boltzmann sigmoid and generalized linear modeling.

Methods

We carried out a cross‐sectional correlation study, including 107 adult inpatients, hospitalized for a stroke. We assessed the activity components of toileting, as well as evaluated physical impairment using the Fugl‐Meyer Assessment, impairments in balance using the Berg Balance Scale, cognitive impairments using the Mini‐Mental State Examination and the presence or absence of unilateral spatial neglect or aphasia.

Results

Boltzmann sigmoid modeling showed that the total scores required to obtain a response at 50% of the maximal value for the required components of toileting ranged between 2.691 and 34.962 points, for the components of “wearing pants” and “cutting the toilet paper,” respectively. A generalized linear model showed that the Berg Balance Scale score was a significant predictor for independent performance on most component activities of toileting.

Conclusions

The component of toileting that was easiest to carry out was cutting the toilet paper, and the most difficult was wearing pants. Balance impairment was an independent predictor of independent toileting after stroke. This detailed toileting assessment enabled us to document the most difficult components of toileting, and to assess the motor and process skills required for independent toileting. Geriatr Gerontol Int 2018; 18: 1166–1172 .     

Renal dysfunction after abdominal or thoracic endovascular aortic aneurysm repair: incidence and risk factors

Purpose

To determine the incidence and risk factors of renal dysfunction after abdominal endovascular aortic repair (EVAR) and thoracic endovascular aortic repair (TEVAR).

Materials and methods

The study consisted of 227 patients treated with EVAR and 90 with TEVAR for aortic aneurysms. Parameters, including patients’ background factors, preoperative renal function, contrast dose and aortic wall irregularity on CT images were assessed in relation to postoperative renal dysfunction.

Results

Deterioration of renal function was observed in 33 of 218 patients (15.1%) after EVAR and in 7 of 79 (8.9%) patients after TEVAR. Hemodialysis was required in one patient after EVAR. In EVAR, renal dysfunction correlated with age (p = 0.034) and occlusion of accessory renal artery (p = 0.0001). In TEVAR, renal dysfunction correlated with age (p = 0.021), contrast dose (p = 0.042) and irregularity of the descending aortic wall (p = 0.023). In a multiple regression analysis, postoperative renal dysfunction was correlated with occlusion of accessory renal artery (p = 0.0003) after EVAR, and age (p = 0.02), contrast dose (p = 0.026) and irregularity of the descending aortic wall (p = 0.042) after TEVAR.

Conclusion

Occlusion of accessory renal artery in EVAR, and age, contrast dose and irregularity of the descending aortic wall in TEVAR were considered to be predictors of postoperative renal dysfunction.

     

Effect of LHRH analog on the seminal vesicles evaluated by transrectal sonography

The maximum horizontal area (MHA) of the seminal vesicles was measured in 20 prostatic cancer patients by means of transrectal sonography (TRS) after LHRH analog treatment. MHA of the seminal vesicles changed in parallel to the serum testosterone (T) level and decreased by 11–62%, compared with the baseline after LHRH analog treatment for 4 months. Two different patterns were observed for the change of MHA. In 9 cases, MHA of the seminal vesicles increased transiently and then decreased gradually, while in the other 11 cases, MHA decreased continuously from the beginning with no significant increase. Thus, the direct and dynamic response of the seminal vesicles to the change of serum T level was clarified. © 1993 Wiley-Liss, Inc.     

Quantitation of urinary chlorobenzene metabolites by HPLC: concentrations of 4-chlorocatechol and chlorophenols in urine and of chlorobenzene in biological specimens of subjects exposed to chlorobenzene

Summary A simple method for the determination of 4-chlorocatechol (ClCh, 4-chloro-1,2-benzenediol) and chlorophenols (ClPh), metabolites of monochlorobenzene (ClBz), in urine by high performance liquid chromatography (HPLC) is described. Enzymatic hydrolysates of urine were applied to a stainless-steel column packed with octadecyl-silanized silica gel, and a mixed solution of 20 mM potassium phosphate monobasic : acetonitryl (75:25, v/v) was used as a mobile phase. The procedures for ether extraction and evaporation of extract could be omitted. The accuracy and precision of the present HPLC method were satisfactory. The excretion kinetics of ClCh and p-ClPh were investigated over 35 h after cessation of ClBz inhalation. Proportional relationships between concentrations of ClBz in air and of its metabolites in urine were observed. The slopes of regression lines predicting the levels of ClCh, p-ClPh and total ClPh in urine taken during the last 2 h of exposure to ClBz in air were 6.56, 1.13 and 2.83 mg/g creatinine for 1 ppm ClBz respectively. ClBz in the blood and the end exhaled air of subjects at the end of exposure were identified by gas chromatography (GC) and mass spectrometry. A proportional relationship was observed between the concentration of ClBz in air and that in blood. The validity of the threshold limit value (TLV) for ClBz as evaluated from the subjective and objective symptoms is discussed.     

Diagnostic value of multislice computed tomography for pancreas divisum: assessment with oblique coronal reconstruction images

OBJECTIVES: To assess the capabilities of high-resolution oblique coronal reconstruction images obtained by multislice computed tomography (CT) in diagnosing pancreas divisum. METHODS: This study included 11 patients with and 53 without pancreas divisum confirmed by direct cholangiopancreatography. Two blinded readers retrospectively interpreted oblique coronal reconstruction images with 0.5-mm continuous slices generated from isotropic or nearly isotropic pancreatic phase images with the scrolling mode and assessed the continuity of the ventral pancreatic duct, dorsal pancreatic duct, and main pancreatic duct in the body. The results were correlated with the findings of direct cholangiopancreatography. Other abnormal findings of the pancreatobiliary region on CT were also recorded in patients with pancreas divisum. RESULTS: The sensitivity and specificity of CT for diagnosing pancreas divisum were 100% and 89%, respectively. Computed tomography demonstrated all associated pancreatobiliary diseases. CONCLUSION: High-resolution oblique coronal reconstruction images allow us to make a diagnosis of pancreas divisum by depicting the continuity of the pancreatic ducts.     

Usefulness of D2-40 immunohistochemistry for differentiation between kaposiform hemangioendothelioma and tufted angioma

BACKGROUND: Recent investigations have demonstrated the utility of the monoclonal antibody D2-40 as a marker for lymphatic endothelium. D2-40 can be used on formalin-fixed and paraffin-embedded materials. Our objective was to elucidate, using D2-40 immunohistochemistry, the differences among capillary hemangiomas, and especially between kaposiform hemangioendothelioma (KHE) and tufted angioma (TA). We studied four cases of KHE, nine cases of TA, and 31 cases of other vascular tumors. Antibodies against CD31, CD34, factor VIII-related antigen, and GLUT1 were also applied. RESULTS: In KHE, D2-40 was markedly reactive for three and partially for one of four cases in the peripheral area of Kaposi's sarcoma-like proliferative capillaries and negative in the surrounding dilated vessels. In TA, D2-40 was partially positive in the surrounding dilated vessels and negative in cannonball-like proliferative capillaries. CONCLUSIONS: Our results suggest that D2-40 is a useful antibody for immunohistochemical discrimination between KHE and TA. In addition, the difference of immunostaining pattern of D2-40 is limited to the peripheral area of capillary proliferation and surrounding dilated vessels; therefore, it is suggested that KHE and TA may reflect different stages in the evolution of a single entity. Namely, they may originate from stem cells possessing the characteristics of both lymphatic and blood vessel endothelial lineages.     

Novel complementary peptides to target molecules

We generated an evolutionary computer program that generates complementary peptide (C-pep) sequences, with the potential to interact with a target peptide, by comparing several physico-chemical parameters of each pair of the complementary peptides being analyzed. We generated C-peps to target several molecules. About 30% of synthesized C-peps interfered with the function of their targets. C5a stimulates generation of TNFα and other inflammatory cytokines. Inhibition of C5a should be effective against sepsis, which impairs the status of cancer-bearing patients. One of the inhibitory C-peps of C5a, termed AcPepA, was effective in Cynomolgus monkeys intravenously infused with a lethal dose of bacterial LPS (4 mg/kg) destined to die. The monkeys were rescued by intravenous administration of 2 mg/kg/h of AcPepA. The excellent therapeutic effect of AcPepA is likely to be due to restriction of high mobility group box 1 (HMGB1) surge induced by the effect of C5a on C5L2, which is the second C5a receptor, since the released HMGB1 has the capacity to stimulate TLR4 as an endogeneous ligand resulting in further activation of inflammatory cells to release inflammatory cytokines forming a positive feedback circuit of inflammation.     

Pulmonary infection of Mycobacterium avium-intracellulare complex with simultaneous organizing pneumonia

A 67-year-old woman presented high-grade fever and dyspnea. Sputum culture confirmed Mycobacterium avium-intracellulare complex (MAC). Transbronchial lung biopsies revealed organizing pneumonia (OP) that was rapidly improved with corticosteroid. Five months after onset, a nodule emerged in the right lung. Although MAC was confirmed, the lesion was deemed too small to merit anti-mycobacterial chemotherapy. Four months later, diffuse infiltrates developed on chest X-ray. Bronchoalveolar lavage study identified MAC and exhibited OP patterns. We commenced antimycobacterial chemotherapy. The infiltrates almost completely improved within a month without corticosteroid.