Oral Gonadotropin-Releasing Hormone Antagonist Relugolix Has the Same Effect as Gonadotropin-Releasing Hormone Agonist Injections in Terms of Preparation for Transcervical Resection Myomectomy.

For preparing the optimal condition in transcervical resection (TCR) surgery, gonadotropin-releasing hormone (GnRH) agonist has been utilized. Recently, an oral GnRH antagonist (relugolix) is available and acts directly on GnRH receptor, avoiding flare up and reducing blood E2 levels rapidly. We retrospectively compared the oral GnRH antagonist (n = 14) effect to that of subcutaneous GnRH agonist (n = 19) for the pretreatment of endometrium in TCR myomectomy. Endometrial thickening was determined by intraoperative videos. The color tone of the endometrium in the normal part was assessed by digital image processing. The median duration of the first GnRH agonist injection and the surgery was 67 days (21-136 days), which is significantly longer than that of the oral GnRH antagonist group, 18.5 days (7-157 days P < 0.01). Both the GnRH agonist and antagonist groups did not exhibit prominence in the endometrium. The GnRH antagonist group showed the same degree of whiteness in the normal endometrium as the GnRH agonist group. The oral GnRH antagonist administration could rapidly atrophy the endometrium and create an optimal surgical field for TCR in a short period.

Structural Changes in Skeletal Muscle Fibers after Icing or Heating on Downhill Running in Mice.

An experimental animal model that causes mild structural disorders of skeletal muscles is essential to understand general exercise-induced muscle damage. Thermal stimulations such as icing and heating are commonly used as treatments for muscle injuries in sports. We established a downhill running (DR) protocol that leads to structural muscle disorders without sarcolemmal disruption and directly compared the structural changes produced by icing and heating after DR. Male ddY mice were divided into the DR, DR plus icing (Ice), and DR plus heating (Heat) groups. All mice ran at 20 m/min, -20% grade on a treadmill for a total of 90 min (three rounds of 30 min). In the Ice and Heat groups, an ice pack and a hot pack were, respectively, applied to the exercised triceps brachii muscles for 20 min just after DR. The proportion of myofibers with structural disorders was higher in the Ice group than in the DR and Heat groups at days 1 and 7 after DR. Moreover, the structural disorder of myofibers was slightly improved in the Heat group at day 1 after DR compared with the DR group. These findings suggest that icing treatment might aggravate the structural changes after DR.

Factors associated with adverse pregnancy outcomes in women with antiphospholipid syndrome: A multicenter study.

The aim of this study was to understand the clinical features of antiphospholipid syndrome (APS)-complicated pregnancies and evaluate risk factors for the adverse pregnancy outcomes. This multicenter study evaluated live-birth rates according to therapy modality for APS and risk factors of pregnancy loss in 81 pregnancies. Risk factors for pregnancy complications, including premature delivery before 34 gestational weeks, hypertensive disorders of pregnancy, thrombocytopenia, and light-for-date neonate, were evaluated in 51 women who received low dose aspirin (LDA) plus unfractionated heparin (UFH) and delivered after 24 GW. The live-birth rate in APS pregnancies with LDA+UFH therapy was 92.6%. A multiple logistic regression analysis demonstrated that LDA+UFH therapy decreased the risk of pregnancy loss (OR 0.13, 95%CI 0.03-0.62), and that a history of pregnancy loss despite LDA+UFH therapy increased the risk of pregnancy loss (OR 8.74, 95%CI 1.69-45.2). LDA therapy prior to pregnancy decreased the risk of premature delivery (OR 0.14, 95%CI 0.03-0.69). Positive tests for two or more anti-phospholipid antibodies increased the risks of premature delivery (OR 9.61, 95%CI 1.78-51.8) and thrombocytopenia (OR 4.90, 95%CI 1.11-21.7). Laboratory findings of low complements increased the risk of hypertensive disorders of pregnancy (OR 12.1, 95%CI 1.61-91.0). Standard therapy yielded high live-birth rates. Positive tests for two or more anti-phospholipid antibodies and low complements were associated with adverse pregnancy outcomes. These results have important implications for clinicians.

Multiple muscular variations including tenuissimus and tensor fasciae suralis muscles in the posterior thigh of a human case.

The posterior thigh muscles on the right side of an 81-year-old male cadaver had multiple variations, denoted muscles I-IV. Muscle I originated from the posteromedial surface of the greater trochanter and divided into two muscle bellies. These muscle bellies fused with the long head of the biceps femoris and were innervated by two branches from muscular branches of the semitendinosus and the long head of the biceps. Muscle II separated from the medial surface of the long head of the biceps in the proximal third and fused with the semitendinosus in the distal fourth. Muscle III was a biventer muscle. Its superior belly separated from the medial surface of the long head of the biceps in the distal third. The inferior belly of this muscle fused with the posterior surface of the crural fascia and was innervated by the tibial nerve. Muscle IV separated from the adductor magnus muscle, passed between the long and short heads of the biceps, fused with the inferior belly of muscle III, and was innervated by the muscular branch of the common fibular nerve to the short head of the biceps. Peeling off the epineurium of the muscular branches to the inferior belly of muscle III showed that this nerve fascicle divided from the common trunk with branches to the gastrocnemius and soleus muscles. The inferior bellies of muscle III and muscle IV were thought to be equivalent to the tensor fasciae suralis and tenuissimus muscles, respectively.

Morphological study on the pressure ulcer-like dermal lesions formed in the rat heel skin after transection of the sciatic nerves.

Due to transection of bilateral sciatic nerves, pressure ulcer-like dermal lesion occurred in the hairy skin covering of the heel skin in almost all rats. In the present study, chronological changes of the rat heel skin after the transection were morphologically and immunohistochemically examined. In the heel skin, redness and swelling began by 3days after the operation, and open wound formed by 17days. At the redness and swelling stage, edema extensively occurred in the dermis. At the thickening stage, the epidermis at the pressed site became transiently thicker, and at the whitening stage, rapidly thinner. At these stages, the epidermis in the skin surrounding the pressed site became gradually thicker. At the yellow scar stage, the skin was covered only by necrotic tissues and horny layer. These layers were scratched during walking and turning, and the yellow scar stage became the open wound stage. Inflammatory reaction began at the thickening stage, and at the yellow scar and open wound stages, necrosis, infiltration of inflammatory cells and dilation of small blood vessels were observed. These morphological features are quite similar to those in the human pressure ulcer. These findings suggest that these dermal injuries could compare the human pressure ulcer for medical treatment and depressurization in future study.

Coagulation factors in whole blood collected from pregnant women and stored at 4°C.

The present study aimed to measure the levels of coagulation factors in stored whole blood of pregnant women and to determine their usefulness in treating pregnant women who developed coagulopathy. A prospective study to measure coagulation factors in stored donated whole blood from pregnant and non-pregnant women was conducted. Fibrinogen, FV, FVII, FVIII, FXIII, and von Willebrand factor were measured in blood stored at 4°C for 0, 1, 3, and 5 weeks. All coagulation factors except for factor XIII decreased during storage. Fibrinogen and factor VII in the blood collected from pregnant women gradually decreased over time and their levels were significantly higher after 5 weeks of storage than those of non-pregnant women at week 0. Whole blood donated by pregnant women for autologous blood transfusion and stored at 4°C may be expected being effectively for the prevention of coagulopathy and the treatment of circulatory blood volume loss.

Gross anatomical study on the human myocardial bridges with special reference to the spatial relationship among coronary arteries, cardiac veins, and autonomic nerves.

Coronary arteries are frequently covered by cardiac muscles. This arrangement is termed a myocardial bridge. Previous studies have shown that myocardial bridges can cause myocardial ischemic diseases or cardiac arrhythmia, but the relevant pathogenic mechanisms remain unknown. We examined 60 hearts from Japanese cadavers macroscopically to clarify the spatial relationships among coronary arteries, cardiac veins and autonomic nerves. We found 86 myocardial bridges in 47 hearts from the 60 cadavers examined (78.3%). Next, we dissected out nine hearts with myocardial bridges in detail under the operating microscope. We found no additional branches of coronary arteries on the myocardial bridge surfaces. However, the cardiac veins, which usually accompany the coronary arteries, ran independently on the myocardial bridge surfaces in the same region. Cardiac autonomic nerves comprised two rami: one was associated with the coronary artery under the myocardial bridge and the other ran on the surface of the bridge. Such spatial relationships among the coronary arteries, cardiac veins and cardiac autonomic nerves at the myocardial bridges are quite similar to those in mouse embryo hearts.

Differential diagnosis of pelvic cystic lesions caused by hemorrhage from inflammatory abscess using CT attenuation in women with acute abdomen.

To determine the efficacy of computed tomography (CT) attenuation of cystic lesions measured on an image browsing system to distinguish abscess from hematoma in women with acute abdomen. The medical records of female patients of reproductive age with acute abdomen who were treated over a 7-year period in a single center and who had undergone laparotomy or laparoscopic surgery and preoperative pelvic CT scanning were retrospectively analyzed to identify those with hematoma or abscess cyst formation. Nineteen patients with tubo-ovarian abscess (abscess group) and six patients with hematoma (hematoma group) formation in the pelvis were included in the analysis. The preoperative CT images of the tubo-ovarian cyst were retrospectively investigated on the basis of cyst attenuation. CT attenuation of the cyst measured by both two gynecologists could be used to clearly distinguish inflammatory disease with abscess formation from bleeding disease with hematoma. CT attenuation on a picture archiving and communication system can distinguish hematoma from abscess in women with acute abdomen. This may significantly contribute to making differential diagnosis without interpretation by a medical radiologist.

Intramuscular nerve distribution pattern in the human tibialis posterior muscle.

The human tibialis posterior muscle (TPM) has developed to maintain the foot arches for adopting bipedal locomotion. The insertion tendon of this muscle is U-shaped in a cross section, and the fibular part of the muscle whose muscle fibers originated from the fibula has a unique architecture. To understand the developmental history of the human TPM, distribution pattern of intramuscular nerves was investigated in ten sides of eight cadavers. Muscular branches entering the TPM could be classified into five types according to the distribution pattern in the muscle. The nerves innervating the part deeper to the insertion tendon ran transversely in the medial direction toward the tibia. Muscular branches innervating the fibular part ran medioinferiorly, and in four cases had communicating rami with the nerve innervating the other parts of this muscle. Muscular branches innervating the superficial layer whose muscle bundles originated from the tibia ran laterally toward the fibula. These results suggest that the fibular part might develop from the common primordium of the TPM, and the deeper layer of the muscle might expand laterally during the development to acquire a new attaching space on the interosseous membrane and fibula. The superficial layer might also develop laterally to acquire the additional attaching spaces on the fascia of the flexor digitorum longus muscle and flexor hallucis longus muscle, thus the insertion tendon might become U-shaped. With these measures, the TPM might be able to increase muscle volume to yield stronger power.

Anatomical observations of the human acromioclavicular joint.

The condition of the acromioclavicular joint (ACJ) is considered to be one factor in the etiology of shoulder impingement syndrome, but there are few supporting morphological data. Fifty-two sides of 35 cadavers were investigated macroscopically and histologically using Safranin O, Fast green, and Weigert's iron hematoxylin staining. The ACJs were classified into three major types depending on the presence or absence of the articular disk. In type 1, the articular disk divided the articular cavity completely (n = 2; 3.8%). In type 2, the articular disk was incomplete and divided the joint cavity incompletely (n = 13; 25%). Type 2 was further divided into subtypes 2a and 2b depending on the configurations of the articular facets. In type 3, no articular disk was found in the joint cavity (n = 37; 71.2%). Type 3 was further divided into subtypes 3a, 3b, and 3c depending on the configurations of the articular surfaces. Fewer than half of the ACJ specimens (22/52 or 42.3%) demonstrated an ellipsoid character in which axial rotation was limited. Histological observation revealed that the upper part of the articular disk of the ACJ comprised fibrocartilage while the lower part comprised dense connective tissue. In cases where the ACJ appears to be an ellipsoid joint, its limited axial rotation restricts posterior tilting of the scapula during arm elevation, which could contribute to shoulder impingement syndrome.

Influence of electrical stimulation on calpain and ubiquitin-proteasome systems in the denervated and unloaded rat tibialis anterior muscles.

The influence of electrical stimulation on calpain and ubiquitin-proteasome systems was examined in the denervated and unloaded tibialis anterior muscles of male Wistar rats. Animals were divided into 5 groups: control, denervation, denervation plus electrical stimulation, unloading, and hindlimb unloading plus electrical stimulation groups. Due to denervation and unloading for 14 days, muscle atrophy markedly occurred in the denervated and unloading animals, and the atrophy in the former was significantly more severe than that in the latter. In the denervated muscle, the atrophy was significantly attenuated by the electrical stimulation, but not in the unloaded muscle. Overexpression of calpain-2 and ubiquitinated proteins was observed only in denervated muscles. In the unloaded animals, though the expression level of calpain-2 appeared to be slightly higher than that in the control, the expression level of ubiquitinated proteins was almost the same as that in the control. The overexpression of calpain-1, calpain-2, and ubiquitinated proteins in the denervated muscle was inhibited by the electrical stimulation. However, there was no difference in these expressions between the unloaded and unloaded plus electrical stimulation groups. The mechanism of the preventive effect of the electrical stimulation on muscle atrophy might differ between the denervated and unloaded muscles.

Morphological analysis of the branches of the dorsal pancreatic artery and their clinical significance.

The dorsal pancreatic artery (DP), characterized by a course that crosses behind the proximal part of the splenic vein. It is regarded as clinically important, providing essential distribution to the pancreas. However, the origin of the DP is extremely variable and therefore cannot provide a sufficient basis for identifying it. The DPs of 11 cadavers were investigated in terms of origin, course and distribution. A total of 45 branches of the DP are classified into seven types on the basis of course and distribution. One of these seven types was consistently observed among the specimens: it ran to the right, passed behind the superior mesenteric vein and anterior surface of the posterior part of the head of the pancreas, and then distributed to the uncinate process and the posterior part of the head of the pancreas. Variations in the branching pattern of the DP can be explained from the following perspective: the consistent branch (#5) is the stem of the DP, and other branches originate from it. It is advisable for surgeons to pay attention to this consistent branch of the dorsal pancreatic artery when performing a pancreaticoduodenectomy.

Heat stress promotes skeletal muscle regeneration after crush injury in rats.

Influences of heat stress on skeletal muscle regeneration were examined in experimental rats. After crush injury to the Extensor digitorum longus muscle (EDL) of the left hindlimb, animals were randomly divided into non-heat and heat groups. In the latter, packs filled with hot water (42°C) were percutaneously applied to the injured EDL muscle for 20min to the front of the lower leg, soon after the injury. During the early stages of muscle regeneration, due to the heat stress, secondary degeneration at the injured site progressed faster, and migration of macrophages, proliferation and differentiation of satellite cells were facilitated. At 14 and 28 days after the injury, the ratio of regenerating muscle fibers exhibiting central nuclei in the heat treated group was significantly lower than that in the non-heat group, and cross sectional area in the heat group was evidently larger than that in the non-heat group. Moreover, in the heat group, the ratio of collagen fiber area at 14 and 28 days after the injury was smaller than in the non-heat group. Together, these findings suggest that acceleration of degeneration processes by heat stress soon after injury is likely to promote skeletal muscle regeneration and inhibit collagen deposition.

Fibrinogen concentrate substitution therapy for obstetric hemorrhage complicated by coagulopathy.

AIM: The aim of this study was to assess the efficacy and safety of fibrinogen concentrate therapy for women with obstetric hemorrhage complicated by dilutional or consumptive coagulopathy by retrospectively reviewing the medical records of relevant patients from a single tertiary center. MATERIAL AND METHODS: Eighteen cases of coagulopathy (8 dilutional, 10 consumptive) administered fibrinogen concentrate at our center over the past 5 years for treating hypofibrinogenemia were identified. Hemoglobin levels, platelet counts, fibrinogen levels, prothrombin time, activated partial thromboplastin time, and D-dimer levels were examined before and after fibrinogen substitution. Units of red blood cells, fresh frozen plasma, and pooled platelet concentrates transfused; blood loss volume; patient outcomes; and adverse events were obtained from medical and laboratory records. RESULTS: The overall response to fibrinogen concentrate was considered good in 12 cases, moderate in four, and poor in two. The response rate was good or moderate in 88% (7/8) of dilutional coagulopathy cases and 89% (9/10) of consumptive coagulopathy cases. Fibrinogen levels significantly increased after fibrinogen substitution therapy (approximately 40 mg/L per g fibrinogen concentrate) in both groups. Although prothrombin time and activated partial thromboplastin time improved after substitution, hemoglobin levels, platelet counts, and D-dimer levels remained unchanged. No serious adverse event was causally associated with fibrinogen substitution therapy. CONCLUSION: Fibrinogen concentrate substitution therapy for obstetric hemorrhage increases fibrinogen levels and appears to be effective in managing dilutional or consumptive coagulopathy.

Prenatal diagnosis of complex rearrangement of chromosome 21: The significance of interphase and metaphase fluorescence in situ hybridization and comparative genomic hybridization.

KEY CLINICAL MESSAGE: Maternal serum screening-positive patient had prenatal diagnosis with amniotic fluid, which showed inconsistent results between interphase fluorescence in situ hybridization (three signals of 21q22.13-21q22.2) and G-banding analysis (46,XY). Further analyses proved that the fetus had extremely complex rearrangements of chromosome 21, including the interstitial duplication of Down syndrome critical region.

The combined effect of electrical stimulation and resistance isometric contraction on muscle atrophy in rat tibialis anterior muscle.

Electrical stimulation has been used to prevent muscle atrophy, but this method is different in many previous studies, appropriate stimulation protocol is still not decided. Although resistance exercise has also been shown to be an effective countermeasure on muscle atrophy, almost previous studies carried out an electrical stimulation without resistance. It was hypothesized that electrical stimulation without resistance is insufficient to contract skeletal muscle forcefully, and the combination of electrical stimulation and forceful resistance contraction is more effective than electrical stimulation without resistance to attenuate muscle atrophy. This study investigated the combined effects of electrical stimulation and resistance isometric contraction on muscle atrophy in the rat tibialis anterior muscle. The animals were divided into control, hindlimb unloading (HU), hindlimb unloading plus electrical stimulation (ES), and hindlimb unloading plus the combination of electrical stimulation and resistance isometric contraction (ES+IC). Electrical stimulation was applied to the tibialis anterior muscle percutaneously for total 240 sec per day. In the ES+IC group, the ankle joint was fixed to produce resistance isometric contraction during electrical stimulation. After 7 days, the cross-sectional areas of each muscle fiber type in the HU group decreased. Those were prevented in the ES+IC group rather than the ES group. The expression of heat shock protein 72 was enhanced in the ES and ES+IC groups. These results indicated that although electrical stimulation is effective to prevent muscle atrophy, the combination of electrical stimulation and isometric contraction have further effect.

Pseudoganglion on the connecting branch between the deep branch of the lateral plantar nerve and medial plantar nerve.

The connecting branch between the deep branch of the lateral plantar nerve and medial plantar nerve often has an enlarged site. We investigated these enlarged sites of the connecting branches. We observed the 22 human feet of 20 Japanese cadavers. We investigated the connecting branch macroscopically and histologically. We found the connecting branches between the deep branch of the lateral plantar nerve and medial plantar nerve in 19 feet out of 22 feet. This connecting nerve branch was interposed between the tendon of the flexor hallucis longus and the flexor hallucis brevis, and there enlarged in the anteroposterior direction. After penetration, numbers of fascicles of this connecting branch were increased at the enlarged site. In this region, the connective tissues surrounding the nerve fascicles and vessels were more developed compared with the adjoining sides of this branch. A few fascicles at this enlarged site innervated the first metatarsophalangeal joint capsule. Other nerve fascicles arose from the connecting branch and branched off muscular branches to the flexor hallucis brevis. This branch possibly receives the physical exertion or friction during gait due to its position. Deformity and overload of the foot can cause sensory disorders of the foot, but the anatomical basis for the relationship between the deformity/overload and sensory disorders of the foot is unclear. We discussed that this connecting branch can be a potential cause of pressure neuropathies in the human foot.

Influence of icing on muscle regeneration after crush injury to skeletal muscles in rats.

The influence of icing on muscle regeneration after crush injury was examined in the rat extensor digitorum longus. After the injury, animals were randomly divided into nonicing and icing groups. In the latter, ice packs were applied for 20 min. Due to the icing, degeneration of the necrotic muscle fibers and differentiation of satellite cells at early stages of regeneration were retarded by ∼1 day. In the icing group, the ratio of regenerating fibers showing central nucleus at 14 days after the injury was higher, and cross-sectional area of the muscle fibers at 28 days was evidently smaller than in the nonicing group. Besides, the ratio of collagen fibers area at 14 and 28 days after the injury in the icing group was higher than in the nonicing group. These findings suggest that icing applied soon after the injury not only considerably retarded muscle regeneration but also induced impairment of muscle regeneration along with excessive collagen deposition. Macrophages were immunohistochemically demonstrated at the injury site during degeneration and early stages of regeneration. Due to icing, chronological changes in the number of macrophages and immunohistochemical expression of transforming growth factor (TGF)-ß1 and IGF-I were also retarded by 1 to 2 days. Since it has been said that macrophages play important roles not only for degeneration, but also for muscle regeneration, the influence of icing on macrophage activities might be closely related to a delay in muscle regeneration, impairment of muscle regeneration, and redundant collagen synthesis.

Influence of muscle length on muscle atrophy in the mouse tibialis anterior and soleus muscles.

The tibialis anterior and soleus muscles were fixed at the stretched or shortened positions to examine the influence of muscle length on muscle atrophy. Mice were divided into control (C), hindlimb suspension (HS), hindlimb suspension with ankle joint fixation at the maximum dorsiflexion (HSD), and hindlimb suspension with ankle joint fixation at the maximum plantarflexion (HSP). During the hindlimb suspension, the length of these muscles in the HS and HSP groups was very similar. Fourteen days after the hindlimb suspension, the atrophy of the tibialis anterior muscle in the HS and HSP groups was evidently milder than that in the HSD group, and that in the HS and HSP groups was very similar, suggesting that atrophy of the tibialis anterior muscle might largely depend on muscle length. Atrophy of the soleus muscle in the HSD group was milder than that in the HS and HSP groups, indicating that atrophy of the soleus muscle might also depend on muscle length. But atrophy of this muscle in the HSP group was milder than that in the HS group. These results demonstrate that some factors induced by the joint immobilization might be effective in preventing atrophy of the soleus muscle.