Search

Akira Toga,1,* Ayush Balaji,2,* Shigeki Nagura1 1Department of Orthopedic Surgery, Saiseikai Yokohama-shi Tobu Hospital, Yokohama, Kanagawa, Japan; 2Hull York Medical School, University of York, York, UK*These authors contributed equally to this workCorrespondence: Akira Toga, Department of Orthopedic Surgery, Saiseikai Yokohamashi Tobu Hospital, 3-6-1 Shimosueyoshi, Tsurumi-ku, Yokohama, Kanagawa, 230-8765, Japan, Tel +81-45-576-3000, Fax +81-45-576-3525, Email akira.toga@gmail.comBackground: Peripheral human bite wounds are rarely serious and are typically treated medically, with the most complex cases requiring only minor amputation or excision of the infected site. There are few to no reports documenting the development of purulent tenosynovitis, necrotizing fasciitis, and osteomyelitis from these lesions. Major amputations are required only rarely in these cases.Case Presentation: A 71-year-old woman presented with an uncontrolled infection following a self-inflicted bite wound to her left middle finger. A bacterial culture of the lesion revealed methicillin-resistant Staphylococcus aureus (MRSA). The infection could not be controlled with antibiotics or additional interventions, including debridement and minor amputation. She contracted severe COVID-19 while in the hospital which limited the available treatment options. In an attempt to control the infection, the patient ultimately underwent a major amputation of the distal left forearm. While recovering from the procedure, the patient succumbed to septic shock and cardiopulmonary arrest.Conclusion: The unusual progression of this case may be attributed to the interventions required to treat acute COVID-19 as well as a variety of confounding factors. For example, vasopressors and steroids used to treat severely-ill patients compromise the local and systemic physiologic responses to acute bacterial infection. It is important to reconsider clinical expectations during the pandemic and intervene as early as possible to prevent ongoing damage and clinical deterioration.Keywords: COVID-19, amputation, bite wound, necrotizing fasciitis, gangrene, purulent tenosynovitis, immunocompromised

OBJECTIVE: To examine the effectiveness of Mao-bushi-saishin-to (Ma-Huang-Fu-Zi-Xi-Xin-Tang in Chinese medicine) (Tochimototenkaido Co. Ltd., Osaka, Japan), one of the traditional herbal medicines, against resistant bacterial infection. SETTING: The Nursing Center Himawari, Izumo, Japan DESIGN, PATIENT, AND PREPARATION: Half of the standard dose of Mao-bushi-saishin-to was prescribed for 7 days to one elderly patient with fever and positive C-reactive protein (CRP) levels suffering from drug resistant Pseudomonas aeruginosa. The daily standard dose of Mao-bushi-saishin-to is prepared from 1200 mg of dried extract obtained from three crude drugs, Ephedrae Herba (4 g), Asiasari Radix (3 g), and Aconiti Tuber (1 g). It is certified by the Japanese Ministry of Health and Welfare. RESULTS: The patient's fever and CRP level returned to normal levels. CONCLUSIONS: In cases in which the fever does not fall in response to antibiotics for at least 3 days, half of the standard dose of Mao-bushi-saishin-to for 7 days might be worth trying to induce remission, especially for elder patients. [ABSTRACT FROM AUTHOR]

Copyright of Archiv für Orthopädische und Unfall-Chirurgie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

We encountered a 64-year-old woman who experienced fulminant myocarditis and underwent treatment with veno-arterial extracorporeal membrane oxygenation and Impella CP support. Subsequently, she underwent a device upgrade to Impella 5.5 and received continuous hemodiafiltration for 3 months. During mechanical circulatory support, she developed refractory anemia and thrombocytopenia, leading to a diagnosis of myelodysplastic syndrome. Following the removal of the devices, she no longer required blood transfusions. She received HeartMate 3 left ventricular assist device implantation as a destination therapy indication despite the presence of myelodysplastic syndrome. She was successfully managed by aspirin-free antithrombotic therapy without any hemocompatibility-related adverse events for 4 months after index discharge on foot. We present a patient with a unique and rare presentation, wherein HeartMate 3 was implanted and successfully managed without aspirin to prevent bleeding complications associated with myelodysplastic syndrome., (© 2024. The Japanese Society for Artificial Organs.)

The management of right heart failure during durable left ventricular assist device (LVAD) support remains an unsolved issue so far. We had a 44-year-old male patient who was diagnosed with arrhythmogenic right ventricular cardiomyopathy and received HeartMate 3 LVAD (Abbott, USA) implantation as a bridge-to-transplant indication. The pump speed was adjusted as low as 4500 rpm to avoid the left ventricular narrowing and interventricular septal leftward shift. Riociguat was administered to decrease the afterload of the right ventricle and increase the preload of the left ventricle, in addition to the combination of neurohormonal blockers. Frequent low-flow alarm events eventually disappeared after amlodipine administration, and he was successfully returned to work. We here present a unique management in a patient with right heart failure due to arrhythmogenic right ventricular cardiomyopathy during HeartMate 3 LVAD support., (© 2024. The Japanese Society for Artificial Organs.)

Bacille Calmette-Guérin( BCG) intravesical therapy is an effective and safe treatment for bladder cancer; however, mycotic aneurysms have been reported as a rare complication. Case 1:A 64-year-old man with a history of BCG intravesical therapy underwent emergent thoracic endovascular aortic repair (TEVAR) for a ruptured thoracic aortic aneurysm (TAA). He was diagnosed with BCG infection by hemosputum specimen culture five months later;then, antituberculous therapy was initiated. However, his follow-up computed tomography scan revealed stent-graft infection and new aneurysm formation. Therefore, we performed a repeated TEVAR with abdominal 4-vessel debranching. There was no recurrence of infection for six years while continuing postoperative antituberculous therapy. Case 2:A 72-year-old man who had undergone BCG intravesical therapy underwent TEVAR for a rapidly enlarging mycotic TAA. He received anti-tuberculous therapy for one year with no recurrent infection for one year. TEVAR may be an effective alternative to the open surgical procedure;however, multidisciplinary treatment including anti-tuberculous therapy and careful long-term follow up are required.

We report our experience with aortic valve replacement in a patient with severe aortic stenosis who had self-reported allergies to multiple metals. The patient was a 74-year-old man. He developed palmoplantar pustulosis after using a dental prosthesis, and a patch test revealed reactions to several metals; therefore, he was diagnosed with systemic metal allergy. His condition progressed to severe aortic stenosis, and bioprosthetic aortic valve replacement was planned. The Avalus valve (Medtronic, Minneapolis, MN, USA) was selected for aortic valve replacement, since the patient reported having allergies to several metals. While most devices used in cardiac surgery contain some amount of metal, the Avalus bioprosthetic valve does not contain metal in the stent and has been extremely useful for aortic valve replacement in patients with suspected metal allergies., (© 2021. The Author(s).)

Background: The vast majority of acute closed tendinous mallet injuries are treated with a splint. Very few studies have directly compared splinting versus pinning the distal interphalangeal joint for this injury. The aim of this cohort study is to determine the outcomes of both methods. Methods: A total of 59 patients with acute tendinous mallet injury were retrospectively enrolled (29 patients in conservative treatment and 30 patients in surgical treatment). Conservative treatment was performed using custom-made thermoplastic splint and surgical treatment was conducted with oblique K-wire fixation of the distal interphalangeal (DIP) joint. The DIP joint was immobilized for eight weeks in both treatments. Active ranges of motion of the affected finger and Miller's classification were evaluated postoperatively. Results: The mean extension lag of the DIP joint in the surgical treatment group was significantly better than it was with conservative treatment (2.1° vs 13.8°). Three patients who were noncompliant with the splint showed poor results, while no patients in the surgical treatment group had a poor result. Conclusions: Surgical treatment with K-wire fixation leads to satisfactory results for acute tendinous mallet injury.

Background: There is a consensus that overactivation of the cardiac sympathetic nervous system (CSN) proportionately increases the severity of heart failure and is accompanied by worse prognosis. Because it is unknown whether patients with aortic valve stenosis (AS) have similar CSN activation, we investigated the effect of transcatheter aortic valve implantation (TAVI).Methods and Results:We enrolled 31 consecutive patients with AS treated by TAVI. 123 I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy was performed at baseline and at 2 weeks after TAVI. At baseline, the early heart-mediastinum ratio (H/M) was within normal limits (3.0±0.5), but the delayed H/M was low (2.6±0.6) and the washout rate (WR) was high (34±13%). WR negatively correlated with aortic valve area (r=-0.389, P<0.01) and cardiac output (r=-0.595, P<0.01) and positively correlated with norepinephrine (r=0.519, P<0.01) and log NT-proBNP level (r=0.613, P<0.01). After TAVI, there were significant decreases in the norepinephrine level (366±179 ng/mL vs. 276±125 ng/mL, P<0.01) and WR (34±13 vs. 26±11%, P<0.01)., Conclusions: The WR of MIBG was a useful marker of CSN activity and severity of AS. Immediate improvement of CSN activity after TAVI implied that AS hemodynamics per se enhanced CSN.

Isolated pulmonary valve endocarditis is an extremely rare clinical condition. Here, we report a case of pulmonary valve endocarditis caused by methicillin-resistant Staphylococcus aureus (MRSA). An 84-year-old man with a history of aortic regurgitation and patent foramen ovale was admitted to our hospital due to fever of unknown origin for 4 weeks' duration. MRSA was detected in his blood cultures. Transthoracic echocardiography demonstrated a mobile vegetation attached to the pulmonary valve, moderate to severe aortic regurgitation, and patent foramen ovale with left-to-right shunt. After 30-days' treatment with vancomycin, gentamicin and rifampicin, he defervesced and blood cultures became negative. At surgery, a large vegetation was still attached to the pulmonary valve, but the leaflets remained with minimum damage. Aortic valve replacement, direct closure of the patent foramen ovale, and simple resection of the vegetation were performed. The postoperative course was uneventful.

In this review article, we describe several topics, including the sandwich technique, the transatrial re-endocardialization technique, the limited apical left ventriculotomy approach and device closure. The sandwich technique was introduced for the closure of muscular ventricular septal defects (VSD) by sandwiching the septum between two felt patches placed in the left and right ventricle. This technique requires neither the transection of muscular trabeculae nor ventriculotomy. Although the sandwich technique has resulted in the improvement of surgical outcomes, cases of postoperative cardiac dysfunction have been reported. Multiple smaller VSDs have been closed with transatrial re-endocardialization. Septal dysfunction may be avoided through this technique, in which the septal trabeculae are approximated in two layers of superficial, endocardial running sutures. Recently, a number of reports have recommended a limited apical left ventriculotomy approach. With this technique, a much shorter incision of around 1 cm at the apex of the left ventricle may be sufficient for achieving the complete closure of apical muscular VSDs. The transcatheter or perventricular device closure of muscular VSDs has increasingly been performed with good results. Although favorable early and mid-term results of device closure have been reported, this method is not always safer or less invasive than surgical closure. Long-term evaluations should be performed to determine whether the right and left ventricular functions are affected by treatment with relatively large devices in the heart.

We report a patient who has survived for 13 years after surgical resection of a cardiac malignant lymphoma. A 73-year-old woman underwent partial resection of a tumor occluding the tricuspid valve, which arose from the right atrium. The pathologic diagnosis was diffuse large B cell lymphoma. She was treated with adjuvant chemotherapy for 6 months postoperatively. Since then, she has shown no evidence of recurrence, without any further treatment. To our knowledge, this is the longest surviving case of cardiac malignant lymphoma. The therapeutic strategy for this malignant cardiac tumor is discussed briefly., (Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

This study is the first case report of the treatment of methicillin-resistant Staphylococcus aureus (MRSA) mediastinitis using therapeutic drug monitoring of the serum and wound exudate concentrations of linezolid in a renal dysfunction patient. In the present study, the serum trough concentration of linezolid was maintained between 2 and 7 μg/mL. Therapeutic drug monitoring dosage adjustments may be especially useful in patients with renal dysfunction and severe MRSA infection.

Surgical correction of total anomalous pulmonary venous connection (TAPVC) remains a challenge, with reported early mortality rates of up to 20%. In this review article, we describe several topics, including surgery for neonates, diagnoses with multidetector computed tomography (MDCT), and primary sutureless repair. Several studies have reported mortality rates of around 10%, and demonstrated unchanged hospital mortality in neonates, despite improvement of the overall mortality of cohorts including older patients. Previous reports identified a low body weight at the time of the operation, preoperative pulmonary venous obstruction (PVO), and a prolonged cardiopulmonary bypass time as risk factors for hospital mortality. With the development of new technologies, MDCT has become a good diagnostic modality for use in the pre- and post-operative evaluation. MDCT delineates the drainage site of the vertical vein and the atypical vessel into the systemic vein, and it can also evaluate the existence of obstruction in the vertical vein. Following favorable experiences with post-repair PVO, the indications for sutureless repair as a primary operation have been expanded for infants, including those at risk of developing PVO after the repair of TAPVC. Primary sutureless repair has proven especially useful for difficult patient groups, such as those with congenital PVO, infracardiac TAPVC with small pulmonary veins, or mixed-type TAPVC.

There has been recent emphasis on the importance of an interdisciplinary heart team to allow active communication between physicians and surgeons regarding the management of cardiovascular diseases. Construction of a heart team requires a system that enables doctors to rapidly review patients' data when exchanging opinions. We tried to build up a heart team by sharing patients' data via network attached storage( NAS). We installed a server at the Information Technology Center of the University of Toyama with a high-security firewall and online storage software( Proself) for receipt and transfer of data. Accounts and passwords allowing connection to the file server were allocated to cardiovascular physicians at 18 core hospitals without cardiovascular surgery departments, and they were grouped in Proself for security. All communications are encrypted and file transfer is automatically notified to an internet protocol (IP) address via e-mail when data are uploaded or downloaded. Thus, the hospital sending the data and the type of data can be identified immediately, making it possible to refer to the corresponding image files. Sharing of data via NAS allows cardiovascular physicians and surgeons to communicate safely and effectively, leading to successful building of a heart team.

Papillary muscle rupture is a lethal complication of after acute myocardial infarction. We report the successful surgical management of complete anterolateral papillary muscle rupture associated with cardiogenic shock in an 80-year-old woman. The patient was admitted with the sudden onset of chest pain and dyspnea. After hemodynamics deteriorated rapidly, she was intubated and intra-aortic balloon pump was started immediately. Transthoracic echocardiography revealed severe mitral regurgitation due to complete anterolateral papillary muscle rupture associated with lateral myocardial infarction. Coronary angiography demonstrated complete occlusion of the first obtuse marginal artery. She underwent emergency mitral valve replacement and coronary artery bypass grafting. There were no complications of surgery and she was discharged on postoperative day 35. Rapid preoperative assessment and aggressive surgical management are important to improve the prognosis in this setting.

Regenerative therapy is a new strategy for the end-stage heart failure; however, the ideal cell source has not yet been established for this therapy. We expected that the amnion might be an ideal cell source for cardiac regenerative therapy and that the differentiation potency of the human amnion mesenchymal cells (hAMCs) could be improved by overexpression of Oct4, a key factor that maintains the undifferentiated state. A plasmid vector was made by insertion of the Oct4 open reading frame (ORF) under control of a cytomegalovirus (CMV) promoter (pCMV-hOct4) and transfected into hAMCs by electroporation. The optimum induction time was investigated by comparing the quantity of stem cell-specific mRNAs, cardiac-specific mRNAs, and cardiac-specific proteins with time. hAMCs already expressed cardiac-specific proteins such as Nkx2.5 and Connexin43. After pCMV-hOct4 transfection, endogenous Oct4 mRNA and other stem cell markers showed a transient increase. With 5-azacytidine treatment, quantities of the cardiac-specific mRNAs, such as GATA4 and myosin light-chain-2v (Mlc-2v), were increased significantly. After Oct4 overexpression, the highest expression of cardiac-specific mRNAs and stem cell makers was seen at almost the same time. Furthermore, more mature myocardial contraction proteins were observed when hAMCs were induced at specific optimal times after gene transfection. In conclusion, hAMCs were activated to an undifferentiated state by overexpression of Oct4, and their cardiac differentiation potency was improved. Thus, the single-time transfection of the Oct4 expression vector may be a useful strategy for effective cell therapy. The use of cryopreserved hAMCs in cell therapy still requires more investigation.

Adult cardiomyocytes have little ability to regenerate, thus cardiac regeneration therapy represents a potential method for treating severe heart failure. Human amniotic mesenchymal cells (hAMCs) have the potential to be a useful cell source for cardiac regeneration therapy. We attempted to isolate stem cells from hAMCs and differentiate them into cardiomyocytes. Nanog promoter-Cre plasmid and cytomegalovirus (CMV) promoter-loxP-STOP-loxP-Red-puro(r) plasmid were co-transfected into immortalized hAMCs (iHAMs). Nanog-positive iHAMs were treated with 5-azacytidine (5-aza), trichostatin A (TA), activin A (AA), and bone morphogenetic protein-4 (BMP-4), or co-cultured with murine fetal cardiomyocytes for cardiomyocytes differentiation. Isolated Nanog-positive iHAMs were analyzed by quantitative RT-PCR and immunofluorescent staining before and after differentiation. Expression of Nanog, Oct3/4, Sox2, and Klf4 was significantly higher in Nanog-positive than in Nanog-negative iHAMs. Nanog-positive iHAMs were stained for Nanog and Oct3/4 in the nucleus. Nanog-positive iHAMs treated with 5-aza expressed Nkx2.5, GATA-4, human atrial natriuretic peptide (hANP), cardiac troponin T (cTnT), myocin light chain (Mlc)-2a, Mlc-2v, β-myosin heavy chain (β-MHC), hyperpolarization-activated cyclic nucleotide gated channels (HCN)-4, and inwardly rectifying potassium channels (Kir)-2.1. Although Nanog-positive iHAMs treated with TA, AA, or BMP-4 expressed several cardiac markers, no contraction was observed. Co-cultured Nanog-positive iHAMs with murine fetal cardiomyocytes spontaneously contracted in a synchronized manner and expressed the cardiac markers. In conclusion, Nanog-positive hAMCs with characteristics of stem cells were isolated and differentiated into cardiomyocyte-like cells, suggesting that these isolated hAMCs could be a useful cell source for cardiac regeneration therapy.

Although improved surgical techniques have led to significantly better outcomes of surgery for total anomalous pulmonary venous connection, the risk of progressive pulmonary venous obstruction continues to be a clinical problem. Both obstructed total anomalous pulmonary venous connection and post-repair pulmonary venous obstruction are associated with a significant risk of recurrent obstruction or death, requiring reoperation for stenosis. In general, side to side anastomosis of the pulmonary venous confluence to the functional left atrium has been performed for supracardiac and infracardiac total anomalous pulmonary venous connection. Repair of total anomalous pulmonary venous connection to the coronary sinus invariably involved unroofing the coronary sinus, followed by pericardial patch closure of the atrial septal defect. Recently, sutureless technique has been adopted as the primary operation for the subgroups of patients that are thought to be at high risk for post-repair pulmonary venous obstruction, such as those with total anomalous pulmonary venous connection associated with right isomerism, infracardiac total anomalous pulmonary venous connection with small individual pulmonary veins, or mixed-type total anomalous pulmonary venous connection. Because the sutureless technique does not require direct anastomosis to the confluence, aggressive resection of the obstructed pulmonary venous tissue can be achieved, and surgically induced distortion of the suture line can be avoided, which may help to prevent subsequent pulmonary venous obstruction. Conventional management strategies for recurrent pulmonary venous obstruction have typically been associated with poor outcomes. Recent reports have supported the use of the sutureless technique to treat post-repair pulmonary venous obstruction.

A 63-year-old woman, without a family history of hemophilia, was admitted to our hospital because of subcutaneous bleeding, intramuscular and intra-articular hematoma, and macroscopic hematuria. On routine blood analysis, a prolonged activated partial thromboplastin time, decreased concentration of factor VIII to less than 1%, and a markedly elevated level of factor VIII inhibitor to 14.1 BU/ml were revealed. Diagnosis of acquired hemophilia was made and she was treated with prednisolone and recombinant activated factor VII (rFVIIa). On day 9 of rFVIIa therapy, she was complicated by acute renal failure (ARF) with increasing macroscopic hematuria. Computed tomography revealed bilateral swelling of the kidneys with bleeding and dilatation of the left renal pelvis. Activated prothrombin complex concentrates (aPCC) was administrated in combination with steroid pulse therapy and hydration. The bleeding tendency, including ARF, was improved with aPCC, and she was treated with prednisolone and cyclophosphamide. She is currently in good health and attending an outpatients' clinic. Acquired hemophilia is associated with various underlying conditions, but our patient did not show any previous history. ARF is a rare complication in acquired hemophilia, requiring a non-invasive treatment combination with early induction of immunosuppressive therapy.

Background: Risk factors associated with cerebral infarction within 7 days after off-pump coronary artery bypass grafting require further statistical elucidation., Methods: From January 1997 to July 2006, off-pump coronary artery bypass grafting was performed in 576 patients at Toyama University Hospital. Factors including previous cerebral infarction, lesions in head and neck vessels, preoperative cerebral ischemic symptoms, intraaortic balloon pump use, number of coronary lesions, number of coronary bypasses, sites of coronary bypasses, number of proximal anastomoses in the ascending aorta, use of aortic no-touch procedure, partial aortic clamping, automatic proximal anastomosis devices, and a proximal seal system were compared retrospectively between patients with and without early cerebral infarction. Factors differing between groups were analyzed further by multivariate logistic regression., Results: Ten patients (1.7%) had cerebral infarction within 7 days after surgery. The subjects were divided into two groups, those who had cerebral infarction after surgery (n = 10) and those who did not (n = 566). Factors showing significant intergroup differences were a previous history of cerebral infarction (p < 0.001), preoperative presence of cerebral ischemic symptoms (p < 0.001), vascular lesions in head and neck vessels (p < 0.001), use of partial aortic clamping (p = 0.002), and postoperative atrial fibrillation within 7 days after surgery (p = 0.011). Multiple logistic regression analysis indicated close relationships between previous history of cerebral infarction (odds ratio, 26.6; 95% confidence interval, 2.8 to 251.1; p = 0.004), preoperative presence of cerebral ischemic symptoms plus lesions in head and neck vessels (odds ratio, 22.8; 95% confidence interval 1.8 to 285.7; p = 0.015), and use of partial aortic clamping (odds ratio, 11.1; 95% confidence interval, 1.4 to 85.7; p = 0.021). Postoperative atrial fibrillation within 7 days after surgery (odds ratio, 3.4; 95% confidence interval, 0.7 to 16.5; p = 0.121) was suspected as a risk factor for postoperative cerebral infarction., Conclusions: Multivariate analysis identified independent factors strongly associated with cerebral infarction after off-pump coronary artery bypass grafting, such as partial aortic clamping, presence of cerebral ischemic symptoms plus head and neck vascular lesions, and previous cerebral infarction.

Background: This study examines whether real-time 3-dimensional echocardiography can provide an image resolution to serve as a substitute for optical visualization in performing mitral valve plasty., Methods: Three pigs were used in this study. A 3-dimensional echocardiographic system was evaluated on an epicardial surface. Beating heart mitral valve plasty was performed with a surgical stapler inserted from the apex of the left ventricle using only 3-dimensional echocardiographic visualization., Results: The high-quality images of the mitral valve were obtained with the probe at the epicardial position. However, by inserting the surgical instrument into the left ventricle, an acoustic shadow developed on the images. The images became indistinct because of the acoustic shadow, and operation became difficult. For the mitral valve plasty, an edge-to-edge mitral valve repair was carried out using a stapler (10 mm) under the beating heart. The stapler was confirmed to seize both leaflets evenly in only 1 of the 3 pigs., Conclusions: Real-time 3-dimensional echocardiography provided clear 3-dimensional images of the mitral valve; however, when a surgical instrument was inserted into the left ventricle, an acoustic shadow appeared on the image and made detailed confirmation difficult. Lessening or eliminating the acoustic shadow would be a key point to improve this procedure.

The present study aimed to determine the impact of REM sleep and grooming on the baroreflex stimulus-response curve for renal sympathetic nerve activity (RSNA). At least 3 days before study, Wistar female rats (n= 12) were chronically implanted with catheters to measure systemic arterial pressure (P(a)) and to intravenously infuse vasoactive drugs. In addition, electrodes were placed for measurements of RSNA, electroencephalogram, trapezius electromyogram and electrocardiogram. The baroreflex curve for RSNA was determined by changing P(a) using rapid intravenous infusions of phenylephrine and nitroprusside and then fitted to an inverse sigmoid function curve. REM sleep induced a vertical suppression of the P(a)-RSNA baroreflex curve, which was characterized by significant decreases in the maximum response (by 72.0%, P < 0.05) and the maximum gain (by 4.02% mmHg(-1), P < 0.05) compared with NREM sleep level. Grooming shifted the P(a)-RSNA baroreflex curve upward and to the right, which was associated with increases in the maximum response (by 45.2%, P < 0.05), the minimum response (by 20.7%, P < 0.05) and the pressure at the centering point (by 11.1 mmHg, P < 0.05). These data suggest that the P(a)-RSNA baroreflex curve was shifted acutely and differently in a state-dependent manner during natural sleep and wake cycle in rats.

The purpose of the present study was to determine the relationship between renal sympathetic nerve activity (RSNA) and renal blood flow (RBF) during normal daily activity in conscious, chronically instrumented Wistar rats (n = 8). The animal's behavior was classified as rapid eye movement (REM) sleep, non-REM (NREM) sleep, quiet awake, moving, and grooming states. On average RSNA was lowest during REM sleep, which was decreased by 39.0 +/- 3.2% (P < 0.05) relative to NREM sleep, and rose linearly with an increase in activity level in the order of quiet awake (by 10.9 +/- 1.8%, P < 0.05), moving (by 29.4 +/- 2.9%, P < 0.05), and grooming (by 65.3 +/- 3.9%, P < 0.05) relative to NREM sleep. By contrast, RBF was highest during REM sleep, which was increased by 4.8 +/- 0.7% (P < 0.05) relative to NREM sleep and decreased significantly (P < 0.05) by 5.5 +/- 0.6 and 6.6 +/- 0.5% during moving and grooming states, respectively, relative to NREM sleep. There was a significant (P < 0.05) inverse linear relationship between the percent changes in RSNA and RBF and between those in RSNA and renal vascular conductance. Furthermore, renal denervation (n = 8) abolished the changes in RBF induced by different natural behavioral activities. These results suggest that the changes in RSNA induced by natural behavioral activities had a significant influence on RBF.

To evaluate the relation between hypervascularization and vascular endothelial growth factor (VEGF) in the thyroid glands of patients with Graves disease, 19 Graves disease tissues and 6 normal thyroid tissues were studied by immunohistochemistry, in situ hybridization (ISH), and reverse transcriptase-polymerase chain reaction. The mean microvascular densities per follicle and per millimeter of the thyroid follicles' circumferential length in the Graves disease tissues (mean 3.37 and 13.91) were significantly higher than those in the normal thyroid tissues (mean 2.15 and 7.28) (tied P = .0005, P = .0185, and P < .05, respectively). An antibody against VEGF markedly reacted with hyperplastic follicular cells in Graves disease. The intensity was especially strong in the cells covering papillary growth regions containing accumulated microvessels. By ISH, VEGF messenger RNA (mRNA) signals were also detected in the hyperplastic follicular cells in Graves disease tissues and were especially strong in papillary growth regions. The VEGF receptor-1 (Flt-1) protein and mRNA were observed in endothelial cells of all Graves disease tissues. These findings suggest that hypervascularity in Graves disease tissues is related to upregulated VEGF expression in hyperplastic follicles.

To determine the usefulness of immunohistochemical estimations of growth activity to predict biological behavior of pheochromocytomas (PC), 42 cases of PC (33 adrenal and nine extra-adrenal tumors) were studied by immunohistochemistry using the monoclonal antibody, MIB-1. The mean MIB-1-positive cell rate for all 42 PCs was low (1.4%). The MIB-1-positive cell rates of adrenal PCs were significantly higher in malignant tumors (mean, 3.30%) than in benign tumors (mean, 0.81%) (P = .0184). In extra-adrenal PCs, the difference between benign (mean, 0.44%) and malignant (mean, 5.10%) tumors was also statistically significant (P = .0004). Other clinicopathologic factors, including family history, age, sex, and multiple endocrine neoplasm (MEN) type II status were also examined and were not statistically significant. In conclusion, estimation of the MIB-1-positive cell rate is useful for histologic distinction between benign and malignant pheochromocytomas. Especially, it is important to note that a high MIB-1-positive cell rate (>2%) is highly suggestive of malignancy.

Polymorphs of (R)-1-[2,3-dihydro-1-(2'-methylphenacyl)-2-oxo-5-phenyl-1H-1,4- benzodiazepin-3-yl]-3-(3-methylphenyl)urea (YM022) were investigated. Two crystalline forms (alpha- and beta-forms) of YM022 were confirmed by powder X-ray diffractometry and differential scanning calorimetry. alpha- And beta-forms were obtained by recrystallization from ethanol and ethanol: water (5:1), respectively. Amorphous YM022 was obtained by spray drying of YM022 methanol solution. Since both crystalline and amorphous YM022 were sparingly soluble in water, solubilization of YM022 by solid dispersion and wet grinding methods were performed. In vitro dissolution study and in vivo absorption study in dogs were carried out using spray-dried solid dispersion, heat-treated solid dispersion and mechanical mixture. Spray-dried solid dispersion and heat-treated solid dispersion showed enhanced bioavailability, whereas mechanical mixture showed no improvement.