The neurohypophysial oxytocin and arginine vasopressin system is activated in a knee osteoarthritis rat model.

Osteoarthritis (OA) causes chronic joint pain and significantly impacts daily activities. Hence, developing novel treatment options for OA has become an increasingly important area of research. Recently, studies have reported that exogenous, as well as endogenous, hypothalamic-neurohypophysial hormones, oxytocin (OXT) and arginine-vasopressin (AVP), significantly contribute to nociception modulation. Moreover, the parvocellular OXT neurone (parvOXT) extends its projection to the superficial spinal dorsal horn, where it controls the transmission of nociceptive signals. Meanwhile, AVP produced in the magnocellular AVP neurone (magnAVP) is released into the systemic circulation where it contributes to pain management at peripheral sites. The parvocellular AVP neurone (parvAVP), as well as corticotrophin-releasing hormone (CRH), suppresses inflammation via activation of the hypothalamic-pituitary adrenal (HPA) axis. Previously, we confirmed that the OXT/AVP system is activated in rat models of pain. However, the roles of endogenous hypothalamic-neurohypophysial hormones in OA have not yet been characterised. In the present study, we investigated whether the OXT/AVP system is activated in a knee OA rat model. Our results show that putative parvOXT is activated and the amount of OXT-monomeric red fluorescent protein 1 positive granules in the ipsilateral superficial spinal dorsal horn increases in the knee OA rat. Furthermore, both magnAVP and parvAVP are activated, concurrent with HPA axis activation, predominantly modulated by AVP, and not CRH. The OXT/AVP system in OA rats was similar to that in systemic inflammation models, including adjuvant arthritis; however, magnocellular OXT neurones (magnOXT) were not activated in OA. Hence, localised chronic pain conditions, such as knee OA, activate the OXT/AVP system without impacting magnOXT.

Acute Mono-Arthritis Activates the Neurohypophysial System and Hypothalamo-Pituitary Adrenal Axis in Rats.

Various types of acute/chronic nociceptive stimuli cause neuroendocrine responses such as activation of the hypothalamo-neurohypophysial [oxytocin (OXT) and arginine vasopressin (AVP)] system and hypothalamo-pituitary adrenal (HPA) axis. Chronic multiple-arthritis activates the OXT/AVP system, but the effects of acute mono-arthritis on the OXT/AVP system in the same animals has not been simultaneously evaluated. Further, AVP, not corticotropin-releasing hormone (CRH), predominantly activates the HPA axis in chronic multiple-arthritis, but the participation of AVP in HPA axis activation in acute mono-arthritis remains unknown. Therefore, we aimed to simultaneously evaluate the effects of acute mono-arthritis on the activity of the OXT/AVP system and the HPA axis. In the present study, we used an acute mono-arthritic model induced by intra-articular injection of carrageenan in a single knee joint of adult male Wistar rats. Acute mono-arthritis was confirmed by a significant increase in knee diameter in the carrageenan-injected knee and a significant decrease in the mechanical nociceptive threshold in the ipsilateral hind paw. Immunohistochemical analysis revealed that the number of Fos-immunoreactive (ir) cells in the ipsilateral lamina I-II of the dorsal horn was significantly increased, and the percentage of OXT-ir and AVP-ir neurons expressing Fos-ir in both sides of the supraoptic (SON) and paraventricular nuclei (PVN) was increased in acute mono-arthritic rats. in situ hybridization histochemistry revealed that levels of OXT mRNA and AVP hnRNA in the SON and PVN, CRH mRNA in the PVN, and proopiomelanocortin mRNA in the anterior pituitary were also significantly increased in acute mono-arthritic rats. Further, plasma OXT, AVP, and corticosterone levels were significantly increased in acute mono-arthritic rats. These results suggest that acute mono-arthritis activates ipsilateral nociceptive afferent pathways at the spinal level and causes simultaneous and integrative activation of the OXT/AVP system. In addition, the HPA axis is activated by both AVP and CRH in acute mono-arthritis with a distinct pattern compared to that in chronic multiple-arthritis.

Long-Term Effects of the 2011 Japan Earthquake and Tsunami on Incidence of Fatal and Nonfatal Myocardial Infarction.

This study aimed to examine the long-term effects of the 2011 Japan earthquake and tsunami on the incidence of fatal and nonfatal myocardial infarction (MI). In the present study, the incidence of 2 types of cardiac events was comprehensively recorded. The study area was divided into 2 zones based on the severity of tsunami damage, which was determined by the percentage of the inundated area within the residential area (<10%, low-impact zone and ≥10%, high-impact zone). The standardized incidence ratio (SIR) and 95% CI for both types of cardiac events during the disaster year and the postdisaster years were determined in each zone. During the 4-year period after the disaster, the SIRs for nonfatal MI did not change to a statistically significant extent in either zones. For fatal MI, the SIR was stable during the study period in the low-impact zone. However, in the high-impact zone, the SIR was significantly elevated in the disaster year of 2011 (1.80 [95% CI 1.32 to 2.28]), and this increase was sustained for the following 3 years (2012, 2.06 [1.55 to 2.57]; 2013, 1.99 [1.49 to 2.48]; 2014, 2.12 [1.62 to 2.63]). The SIRs for fatal MI for the 4 postdisaster years in the municipal areas were significantly correlated with the percentage of the inundated area (r = 0.83; p <0.001) and the number of deaths due to the tsunami (r = 0.77; p <0.005) but not with the maximum seismic intensity (r = 0.43; p = 0.12). In conclusion, these results suggest that the devastating tsunami was associated with a continual increase in the incidence of fatal MI among disaster survivors.

Sustained Increase in the Incidence of Acute Decompensated Heart Failure After the 2011 Japan Earthquake and Tsunami.

This study investigated the long-term impact of the 2011 Japan earthquake and tsunami on the incidence of acute decompensated heart failure (HF) in the disaster area. This was a population-based study using comprehensive registration for all hospitals within the study area. The standardized incidence ratio (SIR) and 95% confidence interval (CI) for new onset of HF during the disaster year (2011) and postdisaster years (2012 to 2014) were determined. When SIR were compared between the low- and high-impact areas, as defined by the extent of tsunami inundation in residential areas, SIR showed a significant increase in high-impact areas in 2011 (1.67, 95% CI 1.45 to 1.88) and tended to return to baseline in 2012, the first postdisaster year (1.25, 95% CI 1.06 to 1.43). The rate again increased in 2013 (1.38, 95% CI 1.18 to 1.57) and 2014 (1.55, 95% CI 1.35 to 1.75). In low-impact areas, no such increase was apparent during either the disaster year or the postdisaster years. Mean postdisaster period SIR for municipalities significantly correlated with the percentage of tsunami flooding in residential areas (r = 0.52, p <0.05) and with the percentage of refugees within the population (r = 0.74, p <0.01). There was no significant relation between maximum seismic intensity and mean SIR in these municipalities. In conclusion, these results suggest that the catastrophic tsunami but not the earthquake per se resulted in a prolonged increase in the incidence of HF among the general population living in tsunami-stricken areas.

The Flap Sandwich Technique for a Safe and Aesthetic Skull Base Reconstruction.

For safe and reliable skull base reconstruction combined with repair of cranial bone defects, we introduce the flap sandwich technique in this study. A titanium mesh is often used to repair structural cranial bone defects because it has less donor site morbidity and is easy to handle. However, titanium mesh has disadvantages of exposure and infection postoperatively. To improve surgical outcomes, we applied the flap sandwich technique to 3 cases of skull base reconstruction combined with cranial bone defect repair. Two anterior skull base defects and 1 middle skull base defect were included in this study. The subjects were all women, aged 30, 58, and 62 years. One patient had former multiple craniotomies and another patient had preoperative radiotherapy. The flap sandwich technique involves structural cranial bone reconstruction with a titanium mesh and soft tissue reconstruction with a chimeric anterolateral thigh free flap. First, the dead space between the repaired dura and the titanium mesh is filled with vastus lateralis muscle, and then structural reconstruction is performed with a titanium mesh. Finally, the titanium mesh is totally covered with the adiposal flap of the anterolateral thigh free flap. The muscle flap protects the dead space from infection, and the adiposal flap covers the titanium mesh to reduce mechanical stress on the covered skin and thus prevent the exposure of the titanium mesh through the scalp. By applying this technique, there was no intracranial infection or titanium mesh exposure in these 3 cases postoperatively, even though 2 patients had postoperative radiotherapy. Additionally, the adiposal flap could provide a soft and natural contour to the scalp and forehead region, and this gives patients a better facial appearance even though they have had skull base surgery.

Predictors and impact of time to clinical stability in community-acquired pneumococcal pneumonia.

BACKGROUND: A clinical stability (CS) evaluation is thought to be important in community-acquired pneumonia (CAP) treatment, but evidence concerning the time to CS (TCS) remains lacking. METHODS: Among consecutive patients hospitalized with pneumococcal pneumonia, relationships between TCS and other clinical outcomes were examined, and predictors and a predictive TCS score were derived from patient characteristics on admission. RESULTS: A total of 144 patients were enrolled, including 46% and 27% with moderate and severe pneumonia, respectively, defined by the pneumonia severity index (PSI). The median TCS was 2 days, and was significantly correlated with the length of hospital stay (r = 0.595); a longer TCS was significantly associated with the more presence of poor clinical outcomes and ICU stays (adjusted odds ratios: 1.359 and 1.366, respectively). A multivariate Cox proportional hazard model revealed an absence of bilateral pneumonia (hazard rate (HR): 2.107) or bacteremia (HR: 2.520), and mild or moderate pneumonia (HR: 2.798 and 2.515, respectively, versus severe) as predictors of CS. A predictive score had moderate discriminating power for the prolonged TCS (area under the curve: 0.76), and provided similar predictive values for poor clinical outcomes and ICU stays. A score of 3 or more points indicated the prolonged TCS, with a sensitivity and specificity of 73.3% and 70.9%, respectively. CONCLUSIONS: Because TCS has a significant relationship with other clinical outcomes of pneumococcal CAP, the prediction of TCS might lead to the prevention of complications or an earlier transition to oral therapy. Future studies are warranted to validate these results.

Diagnostic management of patients with suspected ocular sarcoidosis.

BACKGROUND: Ophthalmologists often refer patients with suspected ocular sarcoidosis to pulmonologists for diagnostic examination of sarcoidosis. However, no recommendation has been proposed for managing such patients. This study aims to prospectively evaluate the diagnostic values of examinations and propose the management of patients with suspected ocular sarcoidosis. METHODS: Consecutive patients with suspected ocular sarcoidosis were prospectively investigated according to type of ocular lesions, measurement of serum ACE, and findings of chest radiography, chest CT, bronchoalveolar lavage (BAL) and transbronchial lung biopsy (TBLB). Diagnostic values were calculated on the basis of pathological results. RESULTS: Forty-two patients were included (female, 71.4%; mean age, 56.2±14.8 years), of whom 64.3% was diagnosed with sarcoidosis. Patient characteristics and ocular lesions did not differ significantly, regardless of the presence of sarcoidosis. Chest CT had low specificity and very high sensitivity for detecting sarcoidosis; in contrast, chest radiography and direct findings of bronchofiberscopy had high specificity and low sensitivity. Serum ACE and BAL did not have high diagnostic value. A flow chart was proposed to diagnose sarcoidosis, and this chart reduced the requirement of TBLB to 50% in our population. During the median follow-up of 51 months, 7 patients in the sarcoidosis group (25.9%) developed new lesions. CONCLUSIONS: Application of our flow chart appears to detect avoidable TBLB. Development of a more comprehensive flow chart including survey of ocular findings is warranted.

Associations of proteinuria, fluid volume imbalance, and body mass index with circadian ambulatory blood pressure in chronic kidney disease patients.

BACKGROUND/AIMS: Obesity and hypervolemic status are the main causes of hypertension in patients with chronic kidney disease (CKD). However, it is difficult to differentiate between them. We aimed to assess the associations of body mass index (BMI) and total body water (TBW) with ambulatory blood pressure (ABP). METHODS: Body composition by bioelectrical impedance analysis (BIA) and 24-h ABP were measured in 40 patients with CKD. TBW was assessed using corrected TBWBIA adjusted for body surface area (cTBWBIA) and the TBWBIA/TBWWatson ratio obtained using an anthropometric formula (Watson). RESULTS: Elevated ABP (average 24-h BP ≥ 135/85 mmHg) was noted in 23 patients, who were more likely to have a higher cTBWBIA and TBWBIA/TBWWatson ratio than patients without elevated BP. Patients with nocturnal non-dipping (<10% drop in BP during sleep) were more likely to have a higher TBWBIA/TBWWatson ratio. Proteinuria and the TBWBIA/TBWWatson ratio were significant independent factors for 24-h ABP. BMI had a positive correlation with the cTBWBIA, TBWBIA/TBWWatson ratio and furosemide use. CONCLUSION: Hypertension is dependent on proteinuria and fluid volume imbalance. The TBWBIA/TBWWatson ratio can serve as an indicator of fluid volume-dependent hypertension. BMI is affected by TBW, in which case BMI can become less involved with 24-h ABP.

Usability of the middle temporal vein as a recipient vessel for free tissue transfer in skull-base reconstruction.

In skull-base reconstruction, finding appropriate recipient veins is difficult if the patient has undergone previous craniotomy or requires multiple drainage vessels, because of postoperative scarring and the limited number of veins in the temporal region. Therefore, we have used the middle temporal vein (MTV) to overcome these problems. We examined the presence and caliber of the MTV in 12 patients undergoing skull-base reconstruction. The MTV was identified in all cases and used for reconstruction, alone or with the superficial temporal vein (STV), in 8 patients without postoperative flap loss and was only measured in 4 patients. The caliber of the MTV was significantly greater than that of the STV, and there was no significant difference between the usage of the MTV and STV in the length of reconstruction time. Therefore, the MTV is of an appropriate caliber, and its use does not require complicated procedures as alternative recipient vessels.

A new concept for classifying skull base defects for reconstructive surgery.

To classify the defects of the skull base, we present a new concept that is intuitive, simple to use, and consistent with subsequent reconstructive procedures. The centers of defects are determined in the anterior (I) or middle (II) skull base. The defects are classified as localized in the defect's center (Ia, IIa) or extended horizontally (Ib, IIb) or vertically (Ic, IIc) from the defect's center. Accompanying defects of the orbital contents and skin are indicated by "O" and "S," respectively. An algorithm for selecting subsequent reconstructive procedures was based on the classification. Using the new system, we retrospectively reclassified 90 skull base defects and examined how the defect classifications were related to the reconstructive flaps used and postoperative complications. All defects were reclassified with the new system without difficulty or omission. The mean correlation rate was high (88%) between the flaps indicated by the new classification and the flaps that had actually been used. The rate of postoperative complications tended to be higher with Ia, Ic, and IIb defects and combined defects. Our new classification concept can be used to classify defects and to help select flaps used for subsequent reconstructive procedures.

Prospective evaluation of the relationship between acute exacerbations of COPD and gastroesophageal reflux disease diagnosed by questionnaire.

BACKGROUND: Little is known about the relationship between acute exacerbations of COPD (AECOPD) and gastroesophageal reflux disease (GERD). The aim of this study was to investigate the effects on AECOPD of GERD diagnosed by a questionnaire. METHODS: The subjects were 221 consecutive patients with stable COPD who were evaluated using the Frequency Scale for Symptoms of GERD (FSSG) and a prospective survey of AECOPD for one year. Patients taking drugs for acid suppression were excluded. The association between the frequency of AECOPD and the presence of GERD or FSSG score was examined. RESULTS: Based on the FSSG, the prevalence of GERD was 26.7%. AECOPD and hospitalization due to AECOPD were significantly more frequent in patients with GERD than in those without GERD, with crude relative risks of 3.42 and 3.66, respectively. Multivariate analyses showed that GERD and COPD stage IV were significant predictors of hospitalization due to AECOPD, independent of respiratory therapies or patient characteristics. The severity of GERD symptoms, as measured by the FSSG score, was significantly correlated with the frequencies of AECOPD and hospitalization due to AECOPD. Similar correlations were seen for the FSSG subscores for acid reflux and gastric dysmotility. CONCLUSIONS: This prospective cohort study showed that GERD appears to be a predictive factor for hospitalization due to AECOPD and that severer GERD symptoms may be associated with more frequent AECOPD. Thus, further studies are warranted to evaluate the preventive effect of the therapy for GERD on AECOPD.

Review of skull base reconstruction using locoregional flaps and free flaps in children and adolescents.

Tumors of the skull base are rare in children, and reconstruction in such patients has rarely been reported. We reviewed 16 cases of skull base reconstruction in patients under 18 years. The study group consisted of 10 boys and 6 girls, whose ages ranged from 2 to 17 years. Of the 16 cases, eight tumors were benign and eight were malignant. Defects were anterior in six cases, lateral in eight cases, and anterolateral in two cases. Reconstruction was performed with locoregional flaps in 11 cases and with free flaps in 5 cases. No significant difference was found between locoregional flaps and free flaps in total operative time, intraoperative blood loss, or postoperative hospital stay. However, in some cases, total operative time, reconstruction time, and blood loss increased to a degree unacceptable for pediatrics. Minor complications occurred in three patients and a major complication occurred in one case. Of four patients, three patients with postoperative complications had undergone chemoradiotherapy. Because of the physical weakness of pediatric patients, complicated reconstructive procedure should be avoided. We believe locoregional flaps will become the first choice for reconstruction. However, if patients have large, complex defects and have received radiotherapy, appropriate free flaps should be used to avoid postoperative complications.