Quality assessment of yellowtail (Seriola quinqueradiata) meat cultured in an offshore floating flexible facility.

Commercial aquaculture of yellowtail (Seriola quinqueradiata) is challenging, owing to deterioration of aquaculture environments. Offshore aquaculture may be a means of overcoming these problems. Here, we assessed the quality of flesh from offshore yellowtail (OY) bred for 1 year in an offshore floating flexible facility compared with coastal yellowtail (CY) cultured simultaneously in a coastal cage facility. The survival rate of the OY group was 94.46%, which was slightly lower than that of CY (98.18%). The feeding rate (feeding weight/fish weight) of CY was 0.4-0.5, whereas that of OY was only 0.3, possibly because poor weather conditions prevented feeding at the offshore facility. However, final fish weights did not differ significantly between both groups. In sensory tests, OY was inferior to CY in terms of oily taste. The lipid content in CY was significantly higher than that in OY. Hardness analysis revealed that OY muscles were harder than those of CY. There were no significant differences between OY and CY in overall sensory evaluations; thus, OY was judged as having equivalent value as a food product with CY. The redness of dark muscles was not significantly different on day 1 of refrigeration. However, the redness value of OY was significantly higher than that of CY on day 2. The inferior fattiness of OY relative to that of CY can be overcome by improving the feeding method. Therefore, offshore aquaculture with negligible environmental pollution may be effective for further development of aquaculture.

Carcinoma of unknown primary origin with isolated adrenal metastasis: a report of two cases.

The adrenal glands are one of the most common sites of malignant tumor metastasis. However, metastatic adrenal carcinoma of unknown primary origin with localized adrenal gland involvement is an extremely rare condition. Herein, we reported two cases of carcinoma of unknown primary origin with isolated adrenal metastasis. In the first case, back pain was the trigger; while in the second case, the triggers were low fever and weight loss. Metabolic abnormalities such as hypertension and obesity were not detected in either case. Neither patient had relevant previous medical histories, including malignancy. However, both had a long-term history of smoking. Systemic imaging studies revealed only adrenal tumors and surrounding lesions. Primary adrenocortical carcinoma was initially suspected, and chemotherapy including mitotane was considered. However, due to difficulty in complete resection of the tumor, core needle tumor biopsies were performed. Histopathological examination of biopsy specimens led to the diagnosis of carcinoma of unknown primary origin with isolated adrenal metastasis. In both cases, additional laboratory testing showed high levels of serum squamous cell carcinoma-related antigen and serum cytokeratin fragment. Malignant lesions confined to the adrenal glands are rare. As in our cases, it could be occasionally difficult to differentiate non-functioning primary adrenocortical carcinoma from metastatic adrenal carcinoma of unknown primary origin localized to the adrenal gland. If the lesion is unresectable and there are elevated levels of several tumor markers with no apparent hormonal excess, core needle tumor biopsy should be considered to differentiate the primary tumor from the metastatic tumor.

Pheochromocytoma crisis with cyclic fluctuation in blood pressure mimics acute coronary syndrome.

SUMMARY: Pheochromocytoma crisis results from the sudden release of large quantities of catecholamines and leads to progressive multiple organ dysfunction. Here we report a case of pheochromocytoma crisis with symptoms associated with acute coronary syndrome (ACS) and severe fluctuations in blood pressure (BP). A 43-year-old Japanese man with hypertension (240/120 mmHg) visited a general hospital for chest pain. Echocardiogram showed ST segment depression and blood test demonstrated elevated troponin T. However, emergent coronary angiography revealed normal findings. CT showed a large adrenal mass on the left side, which was suspected as the cause of chest pain and BP elevation. After the patient was transported to our hospital, his BP was found to oscillate between 70 and 240 mmHg, and level of consciousness was decreased. After hospitalization, he had a further decrease in consciousness, a rise in body temperature, and a gradual increase in the interval between the upper and lower systolic BP. His systolic BP varied between 30 mmHg and 300 mmHg at the intervals of 20-30 min. After a multimodality therapy, including α-blocker and high dose fluid replacement, the fluctuation in his BP was gradually decreased and got stabilized after approximately 24 h. Approximately 3 weeks later, he underwent left adrenalectomy. This case showed that pheochromocytoma with internal necrosis might be misdiagnosed as ACS. Furthermore, in cases with a large adrenal tumor and severe elevation or fluctuations of BP, pheochromocytoma should be suspected and treated with α-blockers and fluid replacements as soon as possible prior to surgery. LEARNING POINTS: High catecholamine levels due to pheochromocytoma crisis might cause symptoms associated with acute coronary syndrome. Adrenal tumor with internal necrosis and the elevation or fluctuations of blood pressure should be suspected to be pheochromocytoma. If pheochromocytoma crisis is suspected, the specialist, such as an endocrinologist or a urologist, should intervene, and an α-blocker treatment with adequate fluid replacement therapy should be initiated as soon as possible. Pheochromocytoma multisystem crisis (PMC) is a fatal condition characterized by multiple organ failure, severe blood pressure variability, high fever, and encephalopathy. This is an extremely rare subtype of a very rare disease such as pheochromocytoma. However, because the fatality rate of PMC is high, clinicians should be aware of the symptoms that mark its onset.

The resonance® metallic ureteral stent in the treatment of malignant ureteral obstruction: a prospective observational study.

BACKGROUND: To study the outcomes and experiences of using metallic stents in treating patients with malignant ureteral obstruction (MUO), we examined the effects of metallic ureteral stenting using the Cook Resonance® stent in the treatment of MUO. METHODS: All patients who had a Resonance metallic stent inserted between April 2015 and March 2018 at one of multiple facilities were prospectively observed with a 1-year follow-up. The primary outcome was the patency rate of the metallic ureteral stent. The secondary outcomes included the complications (e.g., infection and fever). RESULTS: Although stent insertion was attempted in 50 patients, the stent could not be inserted as a ureteral stent in three patients due to severe ureteral stricture, and one ureteral cancer patient was excluded from the analysis. The remaining 46 patients' median age was 67 years (range 28-85 years) (16 males, 30 females). Twenty-four patients died during the study; their median survival time was 226 days. The median follow-up period for the censored patients was 355 days (range 16-372 days), and just seven patients were still alive without Resonance failure > 1 year later. The women's IPSS scores tended to be lower than those of the men. Regarding the OABSS score, although the women's total score tended to be low, the difference between the men's and women's scores was nonsignificant. The bacteria detected from urine culture after stent insertion were more gram-positive than gram-negative. CONCLUSION: Metallic ureteric stenting using the Resonance stent is safe and effective for treating MUO. Subjective symptoms were relatively less in the female patients.

A case of panspinal epidural abscess that presented with meningeal irritation.

Case: In rare cases, spinal epidural abscess involves the entire spine and can lead to neurological deficits and sepsis if treatment is delayed or suboptimal. A 65-year-old man was admitted with a diagnosis of bacterial meningitis. After admission, magnetic resonance imaging showed a spinal epidural abscess from the cervical to lumbar spine. Blood culture revealed Staphylococcus aureus. The patient was initially treated medically because he had no neurological deficits. Repeat blood culture remained positive and abscesses were found in the mediastinum and bilateral psoas muscles. Outcome: Surgery was carried out and the patient's postoperative course was satisfactory. Conclusion: Spinal epidural abscess can extensively affect the spine and may present with the symptoms of bacterial meningitis. It is essential to examine the entire spine and paraspinal regions and to treat early in cases of spinal epidural abscess.

Co-administration of dexamethasone increases severity and accelerates onset day of neutropenia in bladder cancer patients on methotrexate, vinblastine, adriamycin and cisplatin chemotherapy: a retrospective cohort study.

BACKGROUND: Bladder cancer patients receiving methotrexate, vinblastine, adriamycin and cisplatin (MVAC) chemotherapy are co-administered with dexamethasone as an anti-emetic. We examined whether or not dexamethasone affects the severity and onset day of MVAC-induced severe neutropenia. METHODS: This was a retrospective study of bladder cancer patients treated with MVAC chemotherapy with or without dexamethasone as an antiemetic at Kanazawa University Hospital during January 2005 - December 2009. Patients were categorized into three groups; no dexamethasone use (Dex (-)), dexamethasone on day 2 (Dex 1 day), and dexamethasone on days 2, 3 and 4 (Dex multiday). We evaluated the incidence of grade 3/4 neutropenia and the day of onset of first severe neutropenic episode during the first course of MVAC chemotherapy. Logistic regression was used to investigate whether co-administration of dexamethasone was a risk factor for severe neutropenia. RESULTS: Episodes of grade 3/4 neutropenia occurred in 3 out of 6 (50.0%), 11 out of 12 (91.7%) and 6 out of 6 (100%) patients in the Dex (-), Dex 1 day, and Dex multiday groups, respectively. The appearance day of first severe neutropenia in the Dex multiday group (13.2 ± 1.0) was significantly accelerated compared to the Dex (-) group (17.7 ± 2.1). Univariate logistic regression analysis revealed that dexamethasone is a risk factor for severe neutropenia (OR 17.0; 95%CI: 1.3-223.1). CONCLUSIONS: Co-administration of dexamethasone for anti-emesis brings forward the first appearance of neutropenia, and increases the severity of neutropenia, in bladder cancer patients receiving MVAC chemotherapy.

A comparative study on the effectiveness of one-way printed communication versus videophone interactive interviews on health promotion.

INTRODUCTION: We performed a comparative study of a health education programme that was delivered either through one-way communication with printed media, or through interactive videophone interviews. We aimed to ascertain which mode of counselling, when used in combination with telemonitoring, is more effective at lifestyle modification intended to improve health status. METHODS: Participants, who were residents of Kurihara city in Miyagi prefecture, Japan, were randomized into two groups: one group received individualized monthly documented reports (n = 33; 22 females; average age: 67.2 years), and the other received interactive videophone communication (n = 35; 22 females; average age: 65.1 years) for three months. Telemonitoring was conducted on both groups, using a pedometer, weighing scale and a sphygmomanometer. Pre- and post-intervention, anthropometric measurements and blood tests were performed; the participants also completed self-administered questionnaires. RESULTS AND DISCUSSION: The two groups showed similar degrees of health status improvement and satisfaction levels. However, the participants in the videophone group were more aware of improvements in their lifestyles than were the participants in the document group. The individualized printed communication programme was less time-consuming compared to videophone communication. Further studies are needed to formulate a balanced protocol for a counselling-cum-telemonitoring programme that provides optimal health improvement and cost performance with the available human resources.

Significance of the mucinous component in the histopathological classification of colon cancer.

PURPOSE: Mucinous carcinoma is often independently classified as a histological type of colon cancer, but there are currently no established diagnostic criteria. The relationship between the proportions of mucinous components to the oncological outcomes was examined to determine whether mucinous carcinoma should be classified as an independent histological type. METHODS: The study group comprised 1,038 patients with colon cancer. The relationships between the survival rates and recurrence patterns with the mucinous component area ratio (MC area ratio) and clinical variables were evaluated. RESULTS: Tumors were classified into three groups: Group 1 (MC area ratio, 0 %), Group 2 (1-49 %), and Group 3 (≥50 %). Of the 1038 tumors studied, 877 (84 %) were classified as Group 1, 123 (12 %) as Group 2, and 38 (4 %) as Group 3. The tumor size was significantly larger in Group 3, and an increased MC area ratio was significantly related to a higher proportion of right-sided tumors. Among patients with stage II or III disease, stage III disease, poorly differentiated adenocarcinoma, and no adjuvant chemotherapy were poor prognostic factors. There was no relationship between the MC area ratio and the survival or recurrence pattern. CONCLUSION: Mucinous carcinoma does not need to be classified as a separate histological type from ordinary differentiated adenocarcinoma.

Ventricular fibrillation by anaphylaxis following consumption of blue_skinned fish.

Case: Approximately 4_h after eating mackerel sushi, a 65_year_old man developed generalized itchiness and redness, after which he became unresponsive. He went into a state of ventricular fibrillation but after he was defibrillated twice, his heartbeat returned. The electrocardiogram obtained immediately after hospitalization showed some ST_segment depression, but a subsequent electrocardiogram showed improvement. Coronary CT showed no obvious stenosis or plaque in the coronary artery. Outcome: Results of an IgE_RAST test confirmed that the level of allergen_specific IgE for mackerel measured <0.10_UA/mL, while the level for anisakis was 1.91_UA/mL. Conclusions: As for the mechanism leading to cardiac arrest, it is thought that the histamines and leukotrienes released from cardiac mast cells caused a coronary artery spasm (Kounis syndrome). This anaphylactic shock is considered to be a result of anisakis allergy, but in general cases of anaphylaxis resulting from consumption of blue_skinned fish.

PHYSIOLOGIC AIRWAY RESPONSES TO INHALED HISTAMINE AND ACETYLCHOLINE IN PATIENTS WITH MILD ASTHMA AS ANALYZED BY FORCED OSCILLATION.

BACKGROUND AND AIMS: Asthma is a chronic disease characterized by airway inflammation; it is sometimes difficult to diagnose. For clinical diagnosis, forced oscillation technique (FOT) measures airway reactance and resistance. By FOT, we investigated respiratory resistance and ventilation perfusion ratio inequality in adults with mild asthma. METHODS: We examined 58 adult patients with mild asthma having no inhaled corticosteroid treatment, and 10 adult patients with post-infectious prolonged cough. Using a MostGraph-01 FOT instrument, we evaluated these patients before and after bronchial hyperresponsiveness to acetylcholine (ACh) or histamine (Hist). We measured the following conditions: change of resistance at 5Hz (R5) and 20Hz (R20), R5-R20, reactance at 5Hz, frequency of resonance (Fres), low-frequency reactance area (ALX), and forced expiratory volume in 1 second (FEV1). RESULTS: There were significant changes of R5, R20, R5-R20, X5, Fres, ALX after provocations for ACh or Hist in all patients with asthma, but not in patients with post-infectious prolonged cough. We calculated the percent decrease in FEV1 after provocation with ACh or Hist. For Ach, this decrease in FEV1 correlated with changes in R20 and Fres for all patients. For Hist, the percent decrease in FEV1 correlated with changes in R5, R20, Fres, and ALX for all patients. Furthermore, we investigated these correlations in patients with normalized bronchial hyperresponsiveness to ACh or Hist. For Ach, the percent decrease in FEV1 correlated with changes in Fres or R5-R20. For Hist, this decrease in FEV1 correlated with changes in R5, R20, and Fres. ROC analysis was used to evaluate the diagnostic value of the ratio of change of Fres in BHR to Hist. The area under the curve was 0.7808 (95% CI=0.657-0.904). A reasonably high specificity (100.0%) and a high sensitivity (53.8%) with a cut-off point of 1.5 in the ratio before and after of Fres were obtained. CONCLUSION: The changes in FOT parameters (before and after bronchial airway responses) may detect airway resistance and ventilation perfusion ratio inequality even in adult patients with asthma having normalized bronchial hyperresponsiveness to ACh or Hist. That results may be useful for an early diagnosis of asthma.

IgE Abs to Der p 1 and Der p 2 as diagnostic markers of house dust mite allergy as defined by a bronchoprovocation test.

BACKGROUND: Limited information is available regarding the clinical usefulness of measuring the levels of IgE to allergen components from house dust mites (HDMs) in the diagnosis of genuine HDM allergy. METHODS: To evaluate the diagnostic usefulness of measuring levels of serum IgE antibodies (Abs) to allergen components from Dermatophagoides pteronyssinus (DP) as a predictor of immediate asthmatic response (IAR) to bronchoprovocation, we studied 55 DP-sensitized asthmatic patients who underwent a bronchoprovocation test using crude DP extract. The levels of IgE Abs to crude DP, nDer p 1, rDer p 2, and rDer p 10 in patients who showed IAR (n = 41) were compared with those in patients who showed no IAR (n = 14). RESULTS: While the frequencies of positivity for IgE Abs to nDer p 1 and rDer p 2 among the entire study population were 89 and 86%, respectively, all patients with IAR tested positive for both of them with high IgE concentrations. The areas under the receiver operating characteristic curves for IgE to nDer p 1 and rDer p 2 as predictors of IAR were 0.913 and 0.906, respectively. The specificity of IgE to nDer p 1 and rDer p 2 was higher than IgE to crude DP even at low cut-off points. CONCLUSIONS: IgE to nDer p 1 and/or rDer p 2 was highly predictive of allergen-induced IAR. These findings validate the clinical usefulness of measuring the levels of IgE to nDer p 1 and rDer p 2 as a diagnostic tool for genuine HDM allergy.

[Comparison of exhaled nitric oxide levels measured by two offline methods and the NO breath® method in Japan].

BACKGROUND: The fraction of exhaled nitric oxide (FeNO) is a useful marker of eosinophilic airway inflammation in asthmatics. Clinical application of FeNO measurement in Japan is expected increase because the procedure is now covered through health insurance. However, the measurement system used is known to affect FeNO results, and it remains unknown whether results from offline methods correlate with those from traditional online methods, such as NO breath®. METHODS: The study population comprised 48 patients at our hospital. FeNO levels were measured by using two offline methods (Sievers and CEIS) and a standard online method, NO breath® RESULTS: FeNONO breath levels were significantly correlated with FeNOSievers(r=0.875) and FeNOCEIS(r=0.888) levels. FeNONO breath levels were nearly equal to FeNOSievers results (FeNONO breath=1.05×FeNOSievers), but both of these levels were lower (p=0.02) than FeNOCEIS data (FeNONO breath=0.74×FeNOCEIS). A Bland-Altman plot of values obtained by the NO breath® and Sievers methods revealed that the NO breath® result was lower than the Sievers level when FeNO was low but was higher than the Sievers level when FeNO was high. CONCLUSION: Differences exist in the levels of FeNO measurement by three methods (two offline methods and NO breath®): conversion equations are needed to compare the FeNO levels obtained by using these three methods. In addition, NO breath® may be more useful to distinguish asthmatic patients from non-asthmatics, compared with Sievers method.

Urodynamic evaluation before and immediately after robot-assisted radical prostatectomy.

OBJECTIVE: To evaluate continence status and mechanism of urinary incontinence immediately after robot-assisted radical prostatectomy (RARP) by performing urodynamic evaluation. METHODS: A total of 87 patients with localized prostate cancer who underwent RARP were included. Filling cystometry, urethral pressure profilometry, and abdominal leak point pressure (ALPP) tests were performed before and immediately after RARP. RESULTS: The mean urine loss ratio (ULR), calculated by dividing the total urine volume by the weight of urine loss after RARP, was 17.8%. Nerve-sparing (NS) surgery significantly affected ULR compared with non-NS surgery. In the comparison between preoperative and postoperative results, the mean maximal cystometric capacity (MCC) and maximal closure urethral pressure (MUCP) decreased from 341 mL and 84.6 cm H2O to 250 mL and 35.6 cm H2O, respectively. No urine leakage was observed in ALPP test preoperatively; however, urine leakage was observed postoperatively in 75 patients (86%), with a mean ALPP of 47.7 cm H2O. Multivariate analysis revealed that MCC, MUCP, and ALPP after RARP were predictive factors for ULR. Linear correlations were found between ULR and MUCP and between ULR and ALPP after RARP. NS status and MUCP after RARP (r=0.247; P=.021) and the ALPP (r=0.254; P=.018) were significantly correlated. CONCLUSION: In urodynamic evaluation immediately after RARP, MCC, MUCP, and ALPP were found to predictive factors for urinary incontinence. The NS procedure contributed to continence status after RARP.

Plasma free metanephrines in the diagnosis of pheochromocytoma: diagnostic accuracy and strategies for Japanese patients.

Measuring the levels of the plasma free metanephrines (PFMs) represents a recently developed and promising test for the diagnosis of pheochromocytoma in the United States and Europe. As this test has not yet been evaluated in Japan, it is necessary to evaluate the diagnostic efficacy of measuring the levels of PFMs compared with the standard measurement of the urinary excretion of metanephrines (uMNs) whose reliability is well established to detect of pheochromocytoma. A total of 101 Japanese subjects clinically suspected of having pheochromocytoma in were included in this study. Subsequently, we prospectively measured the PFMs levels in all patients, compared with those of biochemical markers of the catecholamine secretion and metabolisms in the plasma and urine. All subjects with adrenal tumors underwent tumor excision. Data were available for 84 of the 101 patients, 47 of whom had histopathologically proven pheochromocytoma and 37 were finally diagnosed with non-pheochromocytoma. The results of comparisons in the accuracy of measurement for diagnosis of pheochromocytoma between PFMs and the urinary excretion of metanephrines (uMNs) were 0.980 VS 0.951 for AUC of receiver operatorating characteristic (ROC) curve, 0.957 VS 0.894 for sensitivity, and 0.973 VS 0.946 for specificity, respectively. Although the differences were small, the results of our study definitely demonstrated that measurement of PFMs was not inferior to standard urinary metanephrines (uMNs) measurement, which is established to be the most reliable biochemical method to detect pheochromocytoma. This study clearly shows measuring the PFMs levels to be a reliable and efficient method for diagnosing pheochromocytoma in Japanese patients, as demonstrated in previous reports.

New molecular diagnostic kit to assess Y-chromosome deletions in the Japanese population.

OBJECTIVES: Deletions in the azoospermia factor regions are the most common known molecular genetic cause of human male infertility involving spermatogenetic failure. Testing for these deletions in Japanese DNA samples using conventional sequence-tagged site probes occasionally lead to considerable non-specific or faint products in the Japanese population. The aim of the present study was to evaluate the sensitivity and specificity of a newly developed kit for the detection of azoospermia factor microdeletions in the Japanese population. METHODS: Sequence-tagged site probes were reselected and the Luminex suspension array assay was carried out. Validation was retrospectively carried out with 2014 DNA sequences with known microdeletions, which were divided into four categories. RESULTS: Category 1 deletions that corresponded to the conventional classification of azoospermia factor deletion were present in 83 men (4.2%), which can result in intrachromosomal homologous recombination. Kit data confirmed the presence of deletions of this type in DNA sequences known to harbor the azoospermia factor deletions. Category 2 deletions involved cytogenetic abnormalities in 28 men (1.4%), whereas category 3 deletions in 759 men (37.7%) were atypical classifications including the gr/gr deletion. As these deletions are thought to be a result of palindromic units and non-homologous recombination, these microdeletions might impact in the interpretation of some clinical findings. The rest of the 1145 cases (56.8%) were assigned to category 4 as normal variants (polymorphism/no deletion). CONCLUSIONS: The present findings show that this new kit offers good sensitivity and specificity with the advantage of saving in terms of cost and time.

Comparison of testosterone fractions between Framingham Heart Study participants and Japanese participants.

OBJECTIVES: To determine testosterone fractions in Japanese men and to compare these values with those of Framingham Heart Study participants. METHODS: We enrolled 498 healthy Japanese men. Total testosterone was assayed by liquid chromatography tandem mass spectrometry, sex hormone-binding globulin was assayed by immunoassay and free testosterone was calculated by a laboratory at the Boston Medical Center. Analog-based free testosterone and immunoassay-based total testosterone were determined by immunoassay. We compared mass spectrometry assay-based total testosterone and calculated free testosterone values in the Japanese participants with values in the American Framingham Heart Study third generation cohort. RESULTS: The mean serum mass spectrometry assay-based total testosterone, sex hormone-binding globulin, and calculated free testosterone values were 439.4 ± 167 ng/dL, 65.34 ± 30.61 nmol/L, and 58.75 ± 20.0 pg/mL, respectively. The correlation coefficients with age for mass spectrometry assay-based total testosterone, sex hormone-binding globulin, and calculated free testosterone were 0.0010, 0.5041, and -0.496, respectively. There were no age-related changes in mass spectrometry assay-based total testosterone values in healthy men (P = 0.981), whereas sex hormone-binding globulin and calculated free testosterone levels showed similar age-related changes (P < 0.0001). Serum analog-based free testosterone levels (8.24 ± 2.9 pg/mL) showed age-related changes (P < 0.0001) regardless of immunoassay-based total testosterone levels (P = 0.828). Serum immunoassay-based total testosterone values (486.1 ± 162.5 ng/dL) correlated with serum mass spectrometry assay-based total testosterone values (r = 0.740, 95% confidence interval 0.6965-0.7781, P < 0.0001). Similarly, analog-based free testosterone and calculated free testosterone values showed a highly significant correlation (r = 0.706, 95% confidence interval 0.6587-0.7473, P < 0.0001). The analog-based free testosterone values were approximately 10% of the calculated free testosterone values. CONCLUSIONS: In contrast to the Framingham Heart Study cohort, total testosterone values in Japanese men are not associated with advancing age; thus, they cannot be used to diagnose late-onset hypogonadism in Japan. The analog-based free testosterone value can be considered instead as a suitable biochemical determinant for diagnosing late-onset hypogonadism syndrome.

Lower Urinary Tract Symptoms are Associated with Erectile Function and Psychological Symptoms in Men with Late-Onset Hypogonadism Syndrome.

OBJECTIVE: We assessed the factors significantly associated with lower urinary tract symptoms (LUTS) in men with late-onset hypogonadism (LOH) syndrome. METHODS: The study population consisted of 258 patients aged 40 years or older diagnosed with LOH syndrome. Each patient completed a questionnaire study, such as the International Index of Erectile Function (IIEF) 5, Aging Male Score (AMS), and International Prostate Symptom Score (IPSS). Body mass index (BMI), waist size, and muscle volume were measured in all patients, and blood biochemical data, including total cholesterol, triglyceride, hemoglobin A1c, and free testosterone (free T), were also collected. We analyzed the factors that have effect on IPSS. RESULTS: The mean age of the patients was 64.9 ± 8.7 years, and the mean free T value was 7.3 ± 2.2 pg/mL. The critical factors affecting IPSS were IIEF5 score, BMI, muscle volume, age, AMS, and free T-value (P < 0.05). Age showed the strongest significant positive correlation with IPSS (r = 0.321, P < 0.001). Each factor was controlled for age. IIEF5 score and AMS were independent factors affecting IPSS (r = -0.221 and 0.195, respectively, P < 0.05). IPSS showed an inverse correlation with IIEF5, and a positive correlation with AMS. LUTS also had a weak negative correlation with Free T-value but this was not significant (r = -0.121, P = 0.061). CONCLUSION: Lower urinary tract symptoms were significantly correlated with erectile function and psychological symptoms in men with LOH syndrome.

Dynamic CCAAT/enhancer binding protein-associated changes of DNA methylation in the angiotensinogen gene.

DNA methylation patterns are maintained in adult somatic cells. Recent findings, however, suggest that all methylation patterns are not preserved. We demonstrate that stimulatory signals can change the DNA methylation status at a CCAAT/enhancer binding protein (CEBP) binding site and a transcription start site and activate expression of the angiotensinogen gene (AGT). A CEBP binding site in the human AGT promoter was hypomethylated in tissues with high expression of AGT, but not in those with low expression. The transcriptional activity of AGT promoter sequences cloned into a reporter plasmid depended on DNA methylation. In cultured human cells, interleukin 6 stimulation caused DNA demethylation around a CEBP binding site and a transcription start site; demethylation was accompanied by increased CEBP-ß recruitment and chromatin accessibility of the AGT promoter. DNA methylation activity decreased in the nucleus. Excess circulating aldosterone upregulated AGT expression and was accompanied by DNA hypomethylation around a CEBP binding site and a transcription start site in human visceral adipose tissue. High salt intake led to upregulation of Agt expression, DNA hypomethylation around 2 CEBP binding sites and a transcription start site, and decreased DNA methylation activity in rat visceral adipose tissue. Taken together, CEBP binding initiates chromatin relaxation and transcription, which are followed by DNA demethylation around a CEBP binding site and a transcription start site in the AGT promoter. Decreased DNA methylation activity in the nucleus may play a role in DNA demethylation. DNA demethylation switches the phenotype of AGT expression from an inactive to an active state.

Effects of dutasteride on lower urinary tract symptoms and general health in men with benign prostatic hypertroplasia and hypogonadism: a prospective study.

INTRODUCTION: We investigated the effects of the relative increase in testosterone by dutasteride administration in patients with benign prostatic hyperplasia and hypogonadism on urinary symptoms or androgen-responsive general health. METHODS: Seventy-six patients were enrolled, and were taking 0.5 mg dutasteride daily for 52 weeks. Before and after treatment, all participants underwent blood test, and body mass index, prostate volume (PV), bone mineral density (BMD), post-voiding residual (PVR) volume, and muscle volume were measured. All patients responded to the questionnaires: International prostatic symptom score (IPSS), Overactive Bladder Symptom score (OABSS). Patients were divided into two groups according to the increase rate of total testosterone (TT): group A, ≥20% increase in TT level; group B, <20% increase or decrease. RESULTS: Baseline TT and free testosterone (FT) levels were significantly lower in group A than group B. Both groups showed marked improvement in PV and PVR. Group A showed significant improvement in IPSS and OABSS with a significant increase of FT level, whereas group B showed no significant change. Dutasteride treatment contributed to a significant increase in BMD in group A. CONCLUSIONS: Dutasteride treatment significantly improved urinary symptoms and BMD in patients with low baseline serum TT and FT levels.

Aberrant methylation of the TDMR of the GTF2A1L promoter does not affect fertilisation rates via TESE in patients with hypospermatogenesis.

Increasing evidence shows a relationship between epigenetic regulation and male infertility. The GTF2A1L gene promoter contains the DNA methylation site of a tissue-specific differentially methylated region (TDMR). Eighty-six patients with non-obstructive azoospermia were assessed for the DNA methylation state of CpG islands in the GTF2A1L promoter using testicular genomic DNA. Based on histological criteria, 26 of the 86 patients had normal spermatogenesis (controls), 17 had hypospermatogenesis and 26 had a Sertoli cell-only phenotype or tubular sclerosis. GTF2A1L TDMR methylation was significantly lower in testes DNA from control samples than from hypospermatogenic samples (P=0.029). Patients with hypospermatogenesis were divided into two subgroups: high DNA methylation (HM, n=5) and low DNA methylation (LM, n=12). The GTF2A1L TDMR methylation rate differed significantly between the HM and LM groups (P=0.0019), and GTF2A1L expression was significantly higher among the LM than in the HM patients (P=0.023). High TDMR methylation was correlated with low GTF2A1L gene expression levels. Both groups demonstrated relatively good outcomes with respect to sperm retrieval, fertilisation, pregnancy and childbirth rates. We observed that aberrant GTF2A1L gene expression was not correlated with fertilisation rates. The testicular sperm extraction (TESE) technique may be used to overcome male infertility due to aberrant TDMR methylation.