TH1/TH2 and regulatory cytokines in adults with otitis media with effusion.

OBJECTIVE: Otitis media with effusion is one of the most common and intractable ear diseases. However, the role of Th1, Th2, and immunoregulatory cytokines on the pathogenesis of the disease in adult patients remains to be determined. The aim of this study is to disclose the cytokine expression in middle ear effusions (MEEs) in adults and to compare the profile on the basis of the presence of allergic rhinitis and the type of effusions. STUDY DESIGN: A prospective controlled clinical study. PATIENTS: MEEs were collected from 80 adult subjects. The concentration of interleukin (IL)-2, IL-4, IL-5, IL-10, IL-12, and interferon (IFN)-gamma in MEEs were determined by using enzyme-linked immunosorbent assay. RESULTS: IL-2, IL-4, IL-5, IL-10, IL-12, and IFN-gamma in MEEs were detected in 60 (75.0%), 33 (41.3%), 42 (52.5%), 14 (17.5%), 80 (100%), and 66 (82.5%) samples, respectively. Among these cytokines, only the concentration of IL-4 in the allergic rhinitis-positive group was significantly higher than that in the allergic rhinitis-negative group. On the other hand, IL-2, IL-12, and IFN-gamma were detected, regardless of the presence of allergic rhinitis, and the concentration of these cytokines correlated with each other. The correlation between the concentration of IL-4 and IL-5 was also detected. In addition, both the incidence rate and the concentration of IL-10 in MEEs were significantly higher in the mucoid type compared with those in the serous type effusions. CONCLUSION: Regardless of allergic status, IL-12 may play a critical role in the pathogenesis of otitis media with effusion by affecting the production of IL-2 and IFN-gamma. In addition, IL-4 may have some impact on the immunologic condition in adults with allergic rhinitis. IL-10 potentially affects the viscosity of MEEs.     

Prolonged oral treatment with an essential amino acid L-leucine does not affect female reproductive function and embryo-fetal development in rats.

L-leucine, an essential amino acid, is one of the most popular ingredients in dietary supplements. To investigate a possibility of its embryo-fetal toxicity in rats, 11- to 12-week old dams were orally administered an aqueous solution of L-leucine at doses of 300 or 1000 mg/kg body weight on gestational days 7-17. Body weight and feed intake was evaluated throughout the whole course of pregnancy (days 0-20). L-Leucine did not influence body weight, but at a dose of 1000 mg/kg, slightly enhanced feed intake on days 14 and 18 of pregnancy. Caesarean section (day 20) revealed no influences on the litter size and weight of live-born fetuses, the number of corpora lutea, implantation index or the quality of placenta, and the minor increase in feed intake was considered irrelevant to the pregnancy outcomes. Fetuses were evaluated in a battery of external, visceral and skeletal examinations. No effects of L-leucine on gender ratio and external abnormalities, and no significant treatment-related variations in visceral and skeletal pathologies were observed. These results suggested that L-leucine, administered orally during organogenesis at doses up to 1000 mg/kg body weight, did not affect the outcome of pregnancy and did not cause fetotoxicity in rats.     

Effects of Upper Body Eccentric versus Concentric Strength Training and Detraining on Maximal Force,Muscle Activation,Hypertrophy and Serum Hormones in Women

Effects of eccentric (ECC) versus concentric (CON) strength training of the upper body performed twice a week for 10 weeks followed by detraining for five weeks on maximal force, muscle activation, muscle mass and serum hormone concentrations were investigated in young women (n = 11 and n = 12). One-repetition bench press (1RM), maximal isometric force and surface electromyography (EMG) of triceps brachii (TB), anterior deltoid (AD) and pectoralis major (PM), cross-sectional area (CSA) of TB (Long (LoH) and Lateral Head (LaH)) and thickness of PM, as well as serum concentrations of free testosterone, cortisol, follicle-stimulating hormone, estradiol and sex hormone-binding globulin were measured. ECC and CON training led to increases of 17.2 ± 11.3% (p < 0.001) and 13.1 ± 5.7% (p < 0.001) in 1RM followed by decreases of -6.6 ± 3.6% (p < 0.01) and -8.0 ± 4.5% (p < 0.001) during detraining, respectively. Isometric force increased in ECC by 11.4 ± 9.6 % (p < 0.05) from week 5 to 10, while the change in CON by 3.9±6.8% was not significant and a between group difference was noted (p < 0.05). Maximal total integrated EMG of trained muscles increased only in the whole subject group (p < 0.05). CSA of TB (LoH) increased in ECC by 8.7 ± 8.0% (p < 0.001) and in CON by 3.4 ± 1.6% (p < 0.01) and differed between groups (p < 0.05), and CSA of TB (LaH) in ECC by 15.7 ± 8.0% (p < 0.001) and CON by 9.7 ± 6.6% (p < 0.001). PM thickness increased in ECC by 17.7 ± 10.9% (p < 0.001) and CON by 14.0 ± 5.9% (p < 0.001). Total muscle sum value (LoH + LaH + PM) increased in ECC by 12.4 ± 6.9% (p < 0.001) and in CON by 7.1 ± 2.9% (p < 0.001) differing between groups (p < 0.05) and decreased during detraining in ECC by -6.5 ± 4.3% (p < 0.001) and CON by -6.1 ± 2.8% (p < 0.001). The post detraining combined sum value of CSA and thickness was in ECC higher (p < 0.05) than at pre training. No changes were detected in serum hormone concentrations, but baseline free testosterone levels in the ECC and CON group combined correlated with changes in 1RM (r = 0.520, p < 0.016) during training. Large neuromuscular adaptations of the upper body occurred in women during ECC, and CON training in 10 weeks. Isometric force increased only in response to ECC, and total muscle sum value increased more during ECC than CON training. However, no changes occurred in serum hormones, but individual serum-free testosterone baseline concentrations correlated with changes in 1RM during strength training in the entire group. Both groups showed significant decreases in neuromuscular performance and muscle mass during detraining, while post detraining muscle sum value was only in ECC significantly higher than at pre training. Key points

• Maximal eccentric and concentric strength training in women for 10 weeks (only twice a week) led to great gains in dynamic strength of upper body.
• Upper body muscle mass increased more after eccentric than concentric strength training.
• During detraining for 5 weeks both groups showed decreases in strength and muscle mass.
• However, post-detraining combined sum muscle mass value was only in ECC higher than at pre-training.

Key words: Muscle force, training, EMG, mass, females, testosterone     

Left Ventricular Abnormality and Covert Atrial Fibrillation in Embolic Stroke of Undetermined Source

Aims: The relationship between left ventricular (LV) function and AF detection in embolic stroke of undetermined source (ESUS) patients with insertable cardiac monitors (ICMs) remains unclear. We investigated the association between LV function and AF detection in patients with ESUS after ICMs implantation. Methods: We enrolled patients with ESUS who underwent ICMs implantation from September 2016 to September 2020 using a single-center, prospective registry. LV systolic and diastolic functions were assessed on precordial echocardiography by LV fractional shortening (LVFS) and average E/e’, respectively. Associations between characteristics of LV function and detection of AF by ICMs were analyzed. Results: Participants comprised 101 patients (median age, 74 years; male, 62%). During a median follow-up period of 442 days (interquartile range (IQR), 202–770 days), AF was detected in 24 patients (24%). Median duration from ICMs implantation to AF detection was 71 days (IQR, 13–150 days). When LVFS and E/e’ were dichotomized by cutoff value, each of low LVFS (＜35.5%; adjusted hazard ratio (HR), 4.77; 95% confidence interval (CI), 1.77–12.9) and high E/e’ (≥ 8.65; adjusted HR, 4.56; 95%CI, 1.17–17.7) were independently associated with AF detection after adjusting for age and sex. When patients were divided into four groups according to dichotomized LVFS and E/e’, the combination of low LVFS and high E/e’ was independently associated with AF. Conclusions: In patients with ESUS after ICMs implantation, the LV characteristics of low LVFS and high E/e’ were associated with AF detection.     

A dose-finding study of glycosylated G-CSF (Lenograstim) combined with CHOP therapy for stem cell mobilization in patients with non-Hodgkin's lymphoma

BACKGROUND: Peripheral blood stem cell (PBSC) reinfusion has been widely used for hematopoietic reconstitution after high-dose chemotherapy. However, the optimal dose of granulocyte colony-stimulating factor (G-CSF) for PBSC mobilization in combination with chemotherapy for autograft remains unknown. METHODS: To find the optimal dose of glycosylated G-CSF (lenograstim) for PBSC mobilization in combination with chemotherapy for aggressive non-Hodgkin's lymphoma (NHL), we conducted a dose-finding study on 43 newly diagnosed patients who had unfavorable prognostic factors. They received four to six courses of cyclophosphamide, doxorubicin, vincristine and prednisolone combined with lenograstim every 2 weeks (biweekly CHOP therapy). PBSC apheresis was started after the third course of biweekly CHOP therapy. Lenograstim was given daily from day 3 until the day of the last apheresis. The optimum dose of lenograstim was assessed based on mobilization efficacy and safety profiles at a daily single dose of 2, 5 and 10 microg/kg for eight patients in each level. RESULTS: The collected number of CD34+ cells in the first apheresis products was higher in the 5 microg/kg group than in the 2 microg/kg group (median, 4.22 x 10(6) vs 2.49 x 10(6) CD34+ cells/kg, P = 0.051). The highest dose of 10 microg/kg (median, 2.99 x 10(6) CD34+ cells/kg) failed to show a dose dependence in PBSC mobilization. The efficacy and safety of the 5 microg/kg dose were further confirmed in an additional 19 patients. CONCLUSIONS: The present study suggests that the recommended dose of lenograstim for PBSC mobilization with CHOP therapy in untreated NHL is 5 microg/kg.     

Intracranial germinoma with syncytiotrophoblastic giant cells in the cerebellopontine angle--case report

A 23-year-old man presented with a 3-week history of left hearing disturbance and left facial nerve paresis. T1-weighted magnetic resonance (MR) imaging showed an iso-intense mass in the left cerebellopontine angle (CPA), with homogeneous enhancement with gadolinium-diethylenetriaminepenta-acetic acid. T2-weighted MR imaging showed the mass as heterogeneously iso- to hyperintense. Gross total removal of the tumor was achieved. Histological examination revealed that the tumor was a germinoma with syncytiotrophoblastic giant cells. Whole central nervous system irradiation with cisplatin-etoposide chemotherapy was performed postoperatively. He has been in good condition with no sign of recurrence for 7 years. Intracranial germ cell tumors in the CPA are very rare. Total surgical removal followed by irradiation and chemotherapy will provide a good outcome.     

Bone mineral density in hypogonadal men remains low after long—term testosterone replacement

AIM: In 11 congenital hypogonadal men, the bone mineral density (BMD) values were determined to assess the effect of long-term androgen replacement therapy (ART) on skeletal integrity. METHODS: Eleven congenital hypogonadal men, including 8 isolated gonadotropin deficiency patients, 2 Kallmann's syndrome and 1 vanishing testes syndrome were recruited and treated with 250 mg of testosterone enanthate intramuscularly every 4 weeks for 7-43 years (mean+/-SD: 21.5 +/-13 years). In these patients and a group of 10 healthy young men (controls), the whole and trabecular BMDs were examined at the distal end of radius by means of a peripheral quantitative computerized tomography device. RESULTS: The whole radial BMD in hypogonadal men was significantly less in the patients than in the healthy men (498+/-115 and 725+/-134 mg/cm(3), respectively; P<0.01); the trabecular BMD was also lower in the hypogonadal men (199+/-80 and 375+/-89 mg/cm(3); P< 0.01). The whole radial BMD values in 10 of 11 hypogonadal men were at least 1 SD below the mean value for healthy young men; 2 hypogonadal men had BMD values more than 2.5 SD lower than the healthy mean. Additionally, the whole radial BMD showed a significant negative correlation with the patient's age at the initiation of ART (r = 0.748, P<0.01). The serum level of bone-specific alkaline phosphatase and the urinary level of deoxypyridinoline were not significantly different between the two groups. CONCLUSION: Osteopenia persists in the hypogonadal men after long-term ART, suggesting that such patients have a persistent defect in bone development not alleviated by androgen replacement.     

Regulation of ER molecular chaperone prevents bone loss in a murine model for osteoporosis

Endoplasmic reticulum (ER) stress response is important for protein maturation in the ER. Some murine models for bone diseases have provided significant insight into the possibility that pathogenesis of osteoporosis is related to ER stress response of osteoblasts. We examined a possible correlation between osteoporosis and ER stress response. Bone specimens from 8 osteoporosis patients and 8 disease-controls were used for immunohistochemical analysis. We found that ER molecular chaperones, such as BiP (immunoglobulin heavy-chain binding protein) and PDI (protein-disulfide isomerase) are down-regulated in osteoblasts from osteoporosis patients. Based on this result, we hypothesized that up-regulation of ER molecular chaperones in osteoblasts could restore decreased bone formation in osteoporosis. Therefore, we investigated whether treatment of murine model for osteoporosis with BIX (BiP inducer X), selective inducer BiP, could prevent bone loss. We found that oral administration of BIX effectively improves decline in bone formation through the activation of folding and secretion of bone matrix proteins. Considering these results together, BIX may be a potential therapeutic agent for the prevention of bone loss in osteoporosis patients.     

Proximal oblique-domed osteotomy of the first metatarsal for the treatment of hallux valgus associate with flat foot: effect to the correction of the longitudinal arch of the foot

Introduction Flat foot and/or metatarsal primus varus are the major causes of hallux valgus, and it is important to correct these deformities in order to prevent the recurrence of this condition. We demonstrate the clinical and radiological assessment of the correction of hallux valgus, metatarsal primus varus, and flat foot after proximal oblique-domed osteotomy of the metatarsus with distal soft tissue reconstruction. Materials and methods Twenty-seven feet of 22 patients with moderate or severe hallux valgus who had undergone proximal oblique-domed osteotomy were studied. After the adductor hallucis tendon was cut at the attachment of the proximal phalanx and at the sesamoid bone, the osteotomy was performed 3 cm dorsal-distal to the metatarsocuneiform joint to transfer distal fragment approximately 5 mm in the plantar direction, and rotated laterally decreasing the first–second intermetatarsal angle to 5 degrees. Results The mean AOFAS score was 54.1 ± 2.8 points at pre-operation and 92.8 ± 4.8 points at the most recent follow-up (P < 0.0001). Significant improvement was seen between the hallux valgus angle (P < 0.0001), first–second intermetatarsal angle (P < 0.0001), first–fifth intermetatarsal angle (P < 0.0001), talar pitch (P = 0.0032), and calcaneal plantar angle (P = 0.0327) before surgery and at one year after surgery. The average improvement of the talar pitch and calcaneal plantar angle was 2.6 ± 1.4 and 2.4 ± 1.5 degrees, respectively. Conclusion This study suggest that proximal oblique-domed osteotomy of the metatarsal as a surgical procedure for the treatment of moderate or severe hallux valgus with flat foot can be recommended to correct the longitudinal arch of the foot and the first–second intermetatarsal angle.