Changes of the permeability of round window membrane in otitis media

The effects of endotoxin, exotoxin, and otitis media on the permeability of the round window membrane (RWM) in chinchillas was investigated by detecting tetraethylammonium chloride, applied to the RWM, using a potassium-selective microelectrode in the scala tympani. The RWM, 48 hours following the application of endotoxin or exotoxin, became significantly more permeable to tetraethylammonium chloride than the normal RWM. Two weeks after the obstruction of the eustachian tube, the permeability of the RWM was decreased. These results suggest that bacterial toxins and the consequential migration of chemical inflammatory mediators act as promotive factors of RWM permeability, and that a pathologic thickness of the RWM and the presence of effusion induced by the obstruction of the eustachian tube acts as an inhibitory factor. In the clinical role of RWM permeability in human otitis media, these two factors must be taken into consideration.     

Hypoadiponectinemia is associated with impaired glucose tolerance and coronary artery disease in non-diabetic men.

BACKGROUND: Impaired glucose tolerance (IGT) is a significant risk factor for cardiovascular disease, but is not always recognized in the clinical setting. An anti-atherogenic adipocytokine, adiponectin, is decreased in type 2 diabetes mellitus, but its role in non-diabetic subjects has not been clarified. The hypothesis investigated in the present study was that plasma adiponectin levels correlate with IGT and coronary artery disease (CAD) in non-diabetic men. METHODS AND RESULTS: Glucose intolerance was evaluated by an oral glucose tolerance test and plasma adiponectin levels were measured in 232 non-diabetic men who underwent coronary angiography. Patients with IGT (n=102) had significantly lower adiponectin levels than those with normal glucose tolerance (n=130) (4.47 [3.23-6.39] vs 5.85 [3.99-8.65] mug/ml, p=0.003). Plasma adiponectin levels were associated with IGT in multiple logistic regression analysis (odds ratio (OR) 0.623, 95% confidence interval (CI) 0.397-0.980; p=0.041). Non-diabetic patients with CAD (n=122) had lower adiponectin levels than those without CAD (n=110) (4.60 [3.32-6.38] vs 6.08 [4.10-9.88] microg/ml, p<0.001). Multiple logistic regression analysis demonstrated adiponectin independently correlated with the presence of CAD (OR 0.432, 95% CI 0.256-0.728; p=0.002). CONCLUSIONS: Hypoadiponectinemia is associated with IGT and CAD in non-diabetic men, suggesting that the adiponectin level can provide valuable information regarding the risk of CAD even in non-diabetic subjects.     

Comparison of tissue pressure and ablation time between the LeVeen and cool-tip needle methods

Background  

Radio frequency ablation (RFA) has been accepted clinically as a useful local treatment for hepatocellular carcinoma (HCC). However, intrahepatic recurrence after RFA has been reported which might be attributable to increase in intra-tumor pressure during RFA. To reduce the pressure and ablation time, we developed a novel method of RFA, a multi-step method in which a LeVeen needle, an expansion-type electrode, is incrementally and stepwise expanded. We compared the maximal pressure during ablation and the total ablation time among the multi-step method, single-step method (a standard single-step full expansion with a LeVeen needle), and the method with a cool-tip electrode. Finally, we performed a preliminary comparison of the ablation times for these methods in HCC cases.     

Isolation of human T-cell leukemia virus type I from a transformed T- cell line derived spontaneously from lymphocytes of a seronegative Egyptian patient with mycosis fungoides

Mycosis fungoides (MF) is a rare form of cutaneous T-cell lymphoma that may be associated with human T-cell leukemia virus type I (HTLV-I) infection. Using the polymerase chain reaction, the HTLV-I pX region was constantly detected in the genomic DNA extracted from peripheral blood mononuclear cells (PBMCs) of an HTLV-I antibody-seronegative Egyptian MF patient enrolled in a study to isolate HTLV-I from North Africa. A CD4+ and interleukin-2 (IL-2) receptor-positive T-cell line was established when the phytohemagglutinin-stimulated PBMCs of that patient were maintained in IL-2-containing culture medium. The cell line (EMF) was initially IL-2 dependent and then became IL-2 independent after gradual withdrawal of the IL-2. The cells reacted positively with monoclonal antibodies specific for the HTLV-I Env or HTLV-I Gag proteins. Using the Southern blot analysis, HTLV-I provirus could be detected in the genomic DNA extracted from the EMF cells. Limited nucleotide sequence of the env region showed more than 95% homology between the EMF provirus and other known HTLV-I isolates. Western blot analysis of the cell lysates showed the expression of the HTLV-I structural proteins. These data imply that a transforming HTLV-I provirus may be present, at least in certain cases of MF, regardless of the presence or absence of the specific antibodies.     

Re-evaluation of antitumor effects of combination chemotherapy with interferon-α and 5-fluorouracil for advanced hepatocellular carcinoma

AIM: To evaluate the efficacy of combination chemotherapy with interferon-alpha (IFNalpha) and 5-fluorouracil (5-FU) in patients with advanced hepatocellular carcinoma (HCC). METHODS: Twenty-eight HCC patients in advanced stage were enrolled in the study. They were treated with IFNalpha/5-FU combination chemotherapy. One cycle of therapy lasted for 4 wk. IFNalpha (3 x 10(6) units) was subcutaneously injected thrice weekly on days 1, 3, and 5 for 3 wk, and 5-FU (500 mg/d) was administered via the proper hepatic artery for 5 consecutive days per week for 3 wk. No drugs were administered during the 4(th) wk. The effect of combination chemotherapy was evaluated in each patient after every cycle based on the reduction of tumor volume. RESULTS: After the 1(st) cycle of therapy, 16 patients showed a partial response (PR, 57.1%) but none showed a complete response (CR, 0%). At the end of therapy, the number of patients who showed a CR, PR, or no response (NR) was 1, 10, and 17, respectively. The response rate for therapy (CR+PR) was 21.5%. Biochemical tests before therapy were compared between responsive (CR+PR) and non-responsive (NR) patients, but no significant differences were found for any of the parameters examined, indicating that no reasonable predictors could be identified in our analysis. CONCLUSION: Attempts should be made to discriminate between responders and non-responders by evaluating tumor size after the first cycle of IFNalpha/5-FU combination chemotherapy. For non-responders, therapy should not proceed to the next cycle, and instead, different combination of anticancer drugs should be explored.     

Rituximab-induced Ileocolitis in a Patient with Gastric MALToma: A Case Report and Literature Review

Rituximab (RTX) is effective for treating cancer, but reports of RTX-associated enterocolitis are limited. We herein report the case of a 65-year-old man who developed RTX-induced ileocolitis. He was diagnosed with gastric mucosa-associated lymphoid tissue lymphoma (MALToma) and treated with RTX. He complained of bloody diarrhea after RTX. Mucosal inflammation on colonoscopy indicated RTX-induced ileocolitis. He was treated with corticosteroids, and his symptoms improved. We reviewed the RTX-associated gastrointestinal adverse events and classified the features into ulcerative colitis, Crohn''s disease, microscopic colitis, and ileocolitis. To our knowledge, this is the first case of a Japanese patient who developed RTX-induced ileocolitis.     

Evidence of Validity for the Japanese Version of the Foot and Ankle Ability Measure

Context:The Foot and Ankle Ability Measure (FAAM) is a valid, reliable, and self-reported outcome instrument for the foot and ankle region.Objective:To provide evidence for translation, cross-cultural adaptation, validity, and reliability of the Japanese version of the FAAM (FAAM-J).Design:Cross-sectional study.Setting:Collegiate athletic training/sports medicine clinical setting.Results:The Activities of Daily Living and Sports subscales of the FAAM-J had correlation coefficients of 0.86 and 0.75, respectively, with the Physical Functioning section of the SF-36 for convergent validity. For divergent validity, the correlation coefficients with Mental Health of the SF-36 were 0.29 and 0.27 for each subscale, respectively. Cronbach α for internal consistency was 0.99 for the Activities of Daily Living and 0.98 for the Sports subscale. A 95% confidence interval with a single measure was ±8.1 and ±14.0 points for each subscale. The test-retest reliability measures revealed intraclass correlation coefficient values of 0.87 for the Activities of Daily Living and 0.91 for the Sports subscales with minimal detectable changes of ±6.8 and ±13.7 for the respective subscales.Conclusions:The FAAM was successfully translated for a Japanese version, and the FAAM-J was adapted cross-culturally. Thus, the FAAM-J can be used as a self-reported outcome measure for Japanese-speaking individuals; however, the scores must be interpreted with caution, especially when applied to different populations and other types of injury than those included in this study.Key Words: self-reported outcome measures, questionnaires, outcome assessments

Key Points

• The Japanese version of the Foot and Ankle Ability Measure (FAAM-J) was successfully translated and cross-culturally adapted.
• Evidence of convergent validity, divergent validity, internal consistency, and test-retest reliability for both subscales of the FAAM-J was obtained.
• The FAAM-J can be used as a self-reported outcome measure for Japanese speakers.

Foot and ankle injuries are common in sport activities. Ankle sprains are the most frequent of all athletic injuries.^1,2 The greatest risk factor for an ankle sprain is a previous ankle sprain, and chronic ankle instability is a concerning and common result of an initial ankle sprain.³ With recurrent injuries, such as ankle sprains, athletes frequently suffer from residual symptoms.^4,5Outcome measures are essential to evidence-based practice because they offer a basis for clinical decisions.^6–8 There are 2 types of outcome measures: clinician rated and patient rated.^8,9 Clinician-rated measures are acquired by clinicians and primarily collect information about the disease or injury. Clinician-rated measures address impairments. In contrast, patient-rated measures focus on the data provided by patients, including information about how patients perceive the effect of the disease or injury on their function and participation in Activities of Daily Living (ADL) and sports. Incorporating patient-based outcome measures into health care is imperative to fully appreciate the effect of pathologic conditions on the patient''s overall health.^8,10 A self-reported outcome instrument allows clinicians to incorporate a patient''s values into the medical treatment and to evaluate the effectiveness of interventions from the patient''s perspective.Self-reported outcome instruments can be generic or specific.¹⁰ Specific self-reported outcome instruments address disease, body region, dimension, summary items, and individual measures.¹⁰ Clinicians need to choose a self-reported outcome instrument based on its intended use. However, before a self-reported outcome instrument is used for that purpose, evidence must be provided that includes, among other items, face validity, content validity, construct validity, internal consistency, and reliability.^10–13 Furthermore, a self-reported outcome instrument needs to be translated and cross-culturally adapted if it is to be used in another culture or by speakers of another language.¹⁴More than a dozen self-reported outcome instruments have been developed for the foot and ankle region.^15–17 The original version of the Foot and Ankle Ability Measure (FAAM) is 1 of the 4 instruments that provide evidence of content validity, construct validity, reliability, and responsiveness.^15,16 To our knowledge, the FAAM has been translated into German, Persian, and French.^18–20 Before this writing, it had not been translated into Japanese. Thus, the primary objective of our study was to provide evidence of the validity and reliability of the Japanese version of the FAAM (FAAM-J).     

Mutations and polymorphisms in the human ornithine transcarbamylase (OTC) gene

Ornithine transcarbamylase (OTC) deficiency is the most common inherited disorder of the urea cycle and is transmitted as an X-linked trait. Defects in the OTC gene cause a block in ureagenesis resulting in hyperammonemia, which can lead to brain damage and death. Three previous mutation updates for the OTC gene have been published, in 1993, 1995, and 2002. The most recent comprehensive update, in 2002, contained 244 mutations including 13 nondisease-causing mutations and polymorphisms. This current update reports 341 mutations, of which 93 have not been previously reported, and an additional 29 nondisease-causing mutations and polymorphisms. Out of the 341 mutations, 149 were associated with neonatal onset of hyperammonemia (within the first week of life), 70 were seen in male patients with later onset of hyperammonemia, and 121 were found in heterozygous females (one unknown). Along with the reported mutations, residual enzyme activities and other pertinent clinical information are included whenever available. Most mutations in the OTC gene are specific to a particular family ("private" mutations). They are distributed throughout the gene, with a significant paucity of mutations in the 32 first codons encoding the "leader" peptide (exon 1 and the beginning of exon 2). Almost all mutations in consensus splice sites confer a neonatal onset phenotype. Using the current molecular screening methods, mutations are found in about 80% of the patients. The remaining patients may have mutations in regulatory domains or mutations deep in the introns, which constitute 98.5% of the genomic sequence. In addition, a phenocopy of OTC deficiency caused by mutations in another unknown gene cannot be excluded.     

Down regulation of bisphenol A glucuronidation in carp during the winter pre-breeding season

Environmental pollution by bisphenol A is prevalent in many rivers. The influence of bisphenol A on the reproductive organs of carp has been demonstrated to be serious, especially in the winter pre-breeding season. Although bisphenol A is detoxified as bisphenol A-glucuronide in carp organs, principally the intestine, the seasonal variation in the efficiency of the detoxification is not known. To estimate the seasonal risk of bisphenol A in carp, we investigated seasonal changes in microsomal UDP-glucuronosyltransferase activity toward bisphenol A in male-carp. Seasonal elimination efficiency of bisphenol A was also examined by organ perfusion in everted intestine. No marked seasonal differences were observed in UDP-glucuronosyltransferase activity toward 1-naphthol, but high activity toward sex steroid hormones (testosterone and estradiol) was observed in the winter pre-breeding season. Low UDP-glucuronosyltransferase activity toward bisphenol A was indicated in winter. The addition of bisphenol A into the mucosal fluid of the everted intestine resulted in excretion of bisphenol A into the mucosal side of the intestine as the metabolite, bisphenol A-glucuronide. Excretion of bisphenol A-glucuronide from carp intestine was highest in summer (proximal intestine: 13.3 nmol; middle intestine: 8.3 nmol; distal intestine: 7.9 nmol) and lowest in winter (proximal intestine: 1.0 nmol; middle intestine: 1.0 nmol; distal intestine: 0.9 nmol). These results suggest that metabolism and excretion of bisphenol A in carp hepatopancreas and intestine are impaired by down regulation of UDP-glucuronosyltransferase activity in the winter pre-breeding season.     

Anti-tumor immune response induced by the fractions derived from OK-432, a streptococcal preparation,by using a monoclonal antibody TS-2 that neutralizes the interferon-gamma-inducing activity of OK-432: comparison between the TS-2-binding and TS-2-unbinding fraction

We have previously isolated a lipoteichoic acid (LTA)-related molecule (OK-PSA) from OK-432, a streptococcal agent, by affinity chromatography on a CNBr-activated Sepharose 4B bound TS-2 monoclonal antibody (mAb) that neutralizes the interferon (IFN)-gamma-inducing activity of OK-432. In the current study, we compared the cytokine-inducing and anti-tumor activities of OK-PSA, a TS-2-binding fraction, with those of OK-PTF, a TS-2-unbinding fraction, in order to determine the efficacy of OK-PSA for clinical use in affinity chromatography using TS-2. In the in vitro experiments using human peripheral blood mononuclear cells (PBMCs), OK-PSA markedly induced Th1-type cytokines, while interleukin (IL)-6 and IL-10, Th2-type cytokines, were induced by OK-PTF. Th1-cytokine induction by OK-PTF was not dose-dependent and was suppressed when PBMCs were treated with a high concentration of OK-PTF. In a mouse model, Th1 cytokines were also induced by OK-PSA and Th2 cytokines were induced by OK-PTF. Th2 cytokine-inducing activity of OK-PTF was accelerated in tumor-bearing mice relative to that in healthy mice. Although the anti-tumor effect of OK-PTF was statistically significant, it was much weaker than that of OK-PSA. A significant difference between the anti-tumor effect of OK-PSA and that of OK-PTF was observed (P<0.05). Finally, OK-PSA elicited its cytokine-inducing effect via Toll-like receptor (TLR) 4, whereas OK-PTF-induced signaling was mediated by both TLR2 and TLR4. These findings strongly suggested that the affinity chromatography using TS-2 is a useful strategy to separate the effective component for cancer therapy (OK-PSA) from other components.