Immunocytochemical localization of kisspeptin neurons in the rat forebrain with special reference to sexual dimorphism and interaction with GnRH neurons

Kisspeptin/metastin has been implicated as a critical regulator in luteinizing hormone (LH) secretion and the reproductive system mediating the effect of estrogen on GnRH neurons. In the present study we examined the sex differences in the effects of estrogen on Kiss1/kisspeptin expression in the forebrain by using gonadectomized rats to assess the interaction of kisspeptin and GnRH neurons. Kiss1/kisspeptin cell bodies were abundant in the rostral periventricular area of the third ventricle (RV3P) and the arcuate nucleus (ARC). A few cell bodies were also observed in other portions of the forebrain, i.e. the bed nucleus of the stria terminalis (BST), the paraventricular hypothalamic nucleus (PaAP), the ventromedial hypothalamic nucleus (VMH), and the medial amygdaloid nucleus (MeA). Kisspeptin-immunoreactive fibers were found mainly in the median eminence (ME), the ARC, and the RV3P, but were scarce in the preoptic area (POA), where GnRH neurons are localized. We also found that estrogen triggers expression of the Kiss1 gene and peptide within all the regions except the ARC, and that the effects in the RV3P, BST, PaAP, and VMH are greater in estrogen treated ovariectomized female rat. It is noteworthy that kisspeptin and GnRH neurons were densely associated in the ME but were rarely in contact in the POA. Thus, our results suggest that kisspeptin-positive neurons, except for the ones in the ARC, are related not only to estrogen-positive feedback, but also sex dimorphism, and that kisspeptin regulates GnRH release in the ME rather than the POA.     

Heightened cough response to bronchoconstriction in cough variant asthma

Background and objective: The pathophysiology of cough variant asthma (CVA) is poorly understood. We compared bronchoconstriction‐triggered cough between CVA patients and normal control (NC) subjects. Methods: There were two protocols in the study. We measured bronchial responsiveness to methacholine (MCh) and counted the number of coughs in nine CVA patients and seven NC subjects (Study A). Using partial and full flow–volume curves, expiratory flow of the partial flow–volume curve at 40% above residual volume level (PEF40) and FEV₁ were used to measure bronchoconstriction. Mild bronchoconstriction was defined as a 35% fall in PEF40 (PC₃₅‐PEF40), and more severe bronchoconstriction as a 20% fall in FEV₁ (PC₂₀‐FEV₁). In study B, the same measurements were obtained in six CVA patients before and after therapy. Results: In study A, more coughs were provoked at PC₃₅‐PEF40 in CVA patients (median, 60 coughs/32 min post challenge; range, 12–135) than in NC subjects (median, 0/32 min; range, 0–13; P < 0.05). At PC₂₀‐FEV₁, more coughs were provoked in CVA patients (median, 60/32 min; range, 12–150) than in NC subjects (median, 20/32 min; range, 0–54; P < 0.05). In study B, the six CVA patients who underwent re‐examination after treatment had less coughs at PC₃₅‐PEF40 (median, 3/32 min; range, 0–14) and PC₂₀‐FEV1 (median, 13/32 min; range, 3–26) after therapy than before therapy (median, 54/32 min; range, 33–125 and 52/32 min, 45–96, respectively; P < 0.05). Conclusions: We identified heightened cough response to bronchoconstriction as a feature of CVA.     

Combination of hepatitis B viral antigens and DNA for prediction of relapse after discontinuation of nucleos(t)ide analogs in patients with chronic hepatitis B

Aim: The factors associated with hepatitis recurrence after discontinuation of nucleos(t)ide analogs (NAs) in patients with chronic hepatitis B were analyzed to predict the risk of relapse more accurately. Methods: A total of 126 patients who discontinued NA therapy were recruited retrospectively. The clinical conditions of a successful discontinuation were set as alanine aminotransferase (ALT) below 30 IU/L and serum hepatitis B virus (HBV) DNA below 4.0 log copies/mL. Results: Relapse of hepatitis B were judged to occur when maximal serum ALT became higher than 79 IU/L or when maximal serum HBV DNA surpassed 5.7 log copies/mL following NA discontinuation since these values corresponded with mean values of ALT (30 IU/L) and HBV DNA (4.0 log copies/mL), respectively. At least 90% of patients with either detectable hepatitis B e antigen or serum HBV DNA higher than 3.0 log copies/mL at the time of NA discontinuation relapsed within one year. In the remaining patients, higher levels of both hepatitis B surface and core‐related antigens at the time of discontinuation, as well as a shorter course of NA treatment, were significantly associated with relapse by multivariate analysis. Conclusions: It appears that negative results for hepatitis B e antigen and serum HBV DNA lower than 3.0 log copies/mL are essential for successful NA discontinuation, which may be attained by a longer treatment period. Levels of hepatitis B surface and core‐related antigens are also significant factors independently associated with relapse of hepatitis.     

Can decompression surgery relieve low back pain in patients with lumbar spinal stenosis combined with degenerative lumbar scoliosis?

Introduction

Decompression with fusion is usually recommended in patients with lumbar spinal stenosis (LSS) combined with degenerative lumbar scoliosis (DLS). However, elderly patients with LSS and DLS often have other comorbidities, and surgical treatment must be both safe and effective. The aim of this study was to investigate whether decompression surgery alone alleviates low back pain (LBP) in patients with LSS and DLS, and to identify the predictors of postoperative residual LBP.

Materials and methods

A total of 75 patients (33 males and 42 females) with a mean age of 71.8 years (range 53–86 years) who underwent decompression surgery for LSS with DLS (Cobb angle ≥ 10°) and had a minimum follow-up period of 1 year, were retrospectively reviewed using the Japanese Orthopaedic Association scoring system for the assessment of lumbar spinal diseases (JOA score). Radiographic measurements included coronal and sagittal Cobb angles, apical vertebral rotation (Nash-Moe method), and anteroposterior and lateral spondylolisthesis. Logistic regression analysis was performed to investigate the predictors of residual LBP after surgery.

Results

Forty-nine patients had preoperative LBP, of which 29 (59.1 %) experienced postoperative relief of LBP. Logistic regression analysis demonstrated that the degree of apical vertebral rotation on preoperative radiography was significantly associated with postoperative residual LBP (odds ratio, 8.16, 95 % confidence interval, 1.55–83.81, p = 0.011).

Conclusion

A higher degree of apical vertebral rotation may therefore be an indicator of mechanical LBP in patients with LSS and DLS. Decompression with fusion should be recommended in these patients.     

The effect of a prostaglandin E1 derivative on the symptoms and quality of life of patients with lumbar spinal stenosis

Background

Quality of life (QOL) is a concern for patients with lumbar spinal stenosis (LSS). In this study, QOL was examined using the 5-item EuroQol (EQ-5D).

Methods

QOL and activities of daily living (ADL) were surveyed for 91 patients who visited 18 medical institutions in our prefecture and were diagnosed with LSS-associated intermittent claudication. A second survey was performed after ≥6 weeks for 79 of the subjects to evaluate therapy with limaprost (an oral prostaglandin E1 derivative) or etodolac (an NSAID). Symptoms, maximum walking time, QOL, ADL items, and relationships among these variables were investigated for all 91 patients. Leg pain, leg numbness, and low back pain while walking were surveyed by use of VAS scores (0–100).

Results

Leg pain, leg numbness, and low back pain while walking (VAS ≥25) were present in 83.5, 62.6, and 54.9 % of the patients in the first survey, and approximately half of the patients had a maximum walking time <15 min. The mean EQ-5D utility value for QOL was 0.59 ± 0.12. This value was significantly associated with maximum walking time (p = 0.030) based on classification of patients into groups with walking times <7.5, 7.5–15, 15–30, and >30 min, showing that maximum walking time affected health-related QOL. Of the 79 patients who completed the second survey, 56 had taken limaprost and 23 (control group) had received etodolac. Limaprost improved possible walking time, reduced ADL interference, and significantly increased the EQ-5D utility score, whereas no significant changes occurred in the control group. Maximum walking time was prolonged by ≥10 min and the EQ-5D utility value was improved by ≥0.1 points in significantly more patients in the limaprost group than in the control group.

Conclusion

According to the findings of this survey, at an average of 8 weeks after administration limaprost improved symptoms, QOL, and ADL in LSS patients whereas treatment with an NSAID reduced pain but did not have any other effects.     

Thoracoscopic esophagectomy while in a prone position for esophageal cancer: a preceding anterior approach method

Background

In 2009, the rate of thoracoscopic esophagectomy for esophageal cancer was about 20 % in Japan. This low rate may be due to the difficulty in maintaining a good surgical field and the meticulous procedures that are required. The purpose of this study was to establish and evaluate a new procedure for performing a thoracoscopic esophagectomy while the patient is in a prone position using a preceding anterior approach to make the esophagectomy easier to perform.

Methods

We have performed thoracoscopic esophagectomy using our new procedure in 60 patients with esophageal cancer. Each patient was placed in a prone position and five trocars were inserted; only the left lung was ventilated and a pneumothorax was maintained. The esophagus was mobilized from the anterior structure during the first step and from the posterior structure during the second step. The lymph nodes around the esophagus were also dissected anteriorly and posteriorly. The patients were sequentially divided into two groups and their clinical outcomes were evaluated.

Results

The mean operative time for the thoracoscopic procedure for the latter 30 cases (203 min) was shorter than that for the former 30 cases (260 min) (P = 0.001). Among the 52 cases without pleural adhesion, the mean blood loss in the latter 26 cases (18 mL) was also less than that in the former 26 cases (40 mL) (P = 0.027). There were no conversions to a thoracotomy and no operative deaths in this series. Postoperative complications related to the thoracoscopic procedure occurred in 8 cases (27 %) in the former group and in 4 cases (13 %) in the latter group.

Conclusions

Thoracoscopic esophagectomy with the patient in the prone position using a preceding anterior approach is a safe and feasible procedure. As experience performing the procedure increases, the performance of the procedure stabilizes. This method seems to make the esophagectomy easier to perform.     

NATURAL SKIN REDUCTION AND BREAST RECOVERY USING A TISSUE EXPANDER AFTER ENUCLEATION OF A GIANT BREAST TUMOUR

We report a new use of the tissue expander for reshaping a breast after resection of a giant tumour. After resection of giant fibroadenomas, two patients had expanders inserted into the tissue defect and gradually reduced in size over five months. This facilitated healing and natural skin shrinkage and resulted in a natural shape and size.     

Self-assembled Nano-layering at the Adhesive interface

According to the 'Adhesion-Decalcification' concept, specific functional monomers within dental adhesives can ionically interact with hydroxyapatite (HAp). Such ionic bonding has been demonstrated for 10-methacryloyloxydecyl dihydrogen phosphate (MDP) to manifest in the form of self-assembled 'nano-layering'. However, it remained to be explored if such nano-layering also occurs on tooth tissue when commercial MDP-containing adhesives (Clearfil SE Bond, Kuraray; Scotchbond Universal, 3M ESPE) were applied following common clinical application protocols. We therefore characterized adhesive-dentin interfaces chemically, using x-ray diffraction (XRD) and energy-dispersive x-ray spectroscopy (EDS), and ultrastructurally, using (scanning) transmission electron microscopy (TEM/STEM). Both adhesives revealed nano-layering at the adhesive interface, not only within the hybrid layer but also, particularly for Clearfil SE Bond (Kuraray), extending into the adhesive layer. Since such self-assembled nano-layering of two 10-MDP molecules, joined by stable MDP-Ca salt formation, must make the adhesive interface more resistant to biodegradation, it may well explain the documented favorable clinical longevity of bonds produced by 10-MDP-based adhesives.