Controlling joint instability after anterior cruciate ligament transection inhibits transforming growth factor-beta-mediated osteophyte formation.

OBJECTIVE: Abnormal joint instability contributes to cartilage damage and osteophyte formation. We investigated whether controlling joint instability inhibited chronic synovial membrane inflammation and delayed osteophyte formation and examined the role of transforming growth factor-beta (TGF-ß) signaling in the associated mechanism. DESIGN: Rats (n = 94) underwent anterior cruciate ligament (ACL) transection. Anterior tibial instability was either controlled (CAM group) or allowed to continue (SHAM group). At 2, 4, and 8 weeks after surgery, radiologic, histopathologic, immunohistochemical, immunofluorescent, and enzyme-linked immunosorbent assay examinations were performed to evaluate osteophyte formation and TGF-ß signaling. RESULTS: Joint instability increased cartilage degeneration score and osteophyte formation, and cell hyperplasia and proliferation and synovial thickening were observed in the synovial membrane. Major findings were increased TGF-ß expression and Smad2/3 following TGF-ß phosphorylation in synovial membarene, articular cartilage, and the posterior tibial growth plate (TGF-ß expression using ELISA: 4 weeks; P = 0.009, 95% CI [260.1-1340.0]) (p-Smad2/3 expression density: 4 weeks; P = 0.024, 95% CI [1.67-18.27], 8 weeks; P = 0.034, 95% CI [1.25-25.34]). However, bone morphogenetic protein (BMP)-2 and Smad1/5/8 levels were not difference between the SHAM model and the CAM model. CONCLUSIONS: This study showed that the difference between anterior tibial instability caused a change in the expression level of TGF in the posterior tibia and synovial membrane, and the reaction might be consequently involved in osteophyte formation.

[Stenosis of left coronary artery ostium by a hypoplastic cusp].

Occlusion of a coronary ostium due to fusion of the aortic cusp to the aortic wall is a rare but noteworthy anomaly, because it may cause a sudden death. We report a 9-year-old girl with severe stenosis of the left coronary ostium by the aortic cusp that fused to the aortic wall. The left coronary flow was restored by excision of the adherent left aortic cusp, and aortic valve replacement was performed with the technique of bilateral enlargement of the aortic valve ring (Yamaguchi's method) to prevent prosthesis-patient mismatch in the future. The patient had an uneventful recovery and was discharged 14th postoperative day (POD). Postoperative angiography showed no coronary ostial stenosis.

[Myers technique and patch enlargement of ascending aorta for diffuse supravalvular aortic stenosis].

A 6-year-old boy was diagnosed with aggravation of diffuse supravalvular aortic stenosis (SVAS). The pressure gradient between the sinus of Valsalva and ascending aorta was 48 mmHg. The diameter of the sino-tubular junction was 7 mm and the ascending aorta was hypoplastic. We performed Myers operation because 3 sinus reconstructions had resulted in superior hemodynamics and reductions in both mortality rate and need for reoperation. We avoided using autologous pericardium because of the possibility of shrinkage and aneurysm. We could easily perform patch enlargement of the ascending aorta by selective cerebral perfusion. The postoperative course was excellent and there was no SVAS or aortic regurgitation (AR). A catheterization showed the pressure gradient was 5 mmHg with trivial AR upon follow-up at 1 year.

Experience of Lymphangiography as a Therapeutic Tool for Lymphatic Leakage After Kidney Transplantation.

INTRODUCTION: Lymphatic leakage after kidney transplantation is a relatively frequent complication but sometimes resistant to treatment, and there is no fixed treatment algorithm. The effectiveness of therapeutic lymphangiography for postoperative lymphatic or chyle leakage has been reported, but few reports are available regarding patients who have undergone kidney transplantation. In this study, we report our experience with lymphangiography as a therapeutic tool for lymphatic leakage after kidney transplantation. PATIENTS AND METHODS: Intranodal lymphangiography for lymphatic leakage was performed in 4 patients (3 male, 1 female; age range, 38 to 70 years old) after living kidney transplantation at the Osaka City University Hospital in Japan. The amount of drainage before lymphangiography was 169 to 361 mL/day. The procedure for intranodal lymphangiography was as follows: the inguinal lymph node was punctured under ultrasound guidance, and the tip of the needle was instilled at the junction between the cortex and the hilum, after which Lipiodol was slowly and manually injected. RESULTS: Lymphangiography was technically successful in 3 out of the 4 patients. In all successful cases, the amount of drainage decreased and leakage finally stopped without additional therapy such as sclerotherapy or fenestration. In 2 cases, we were able to directly detect the leakage site using lymphangiography. The time between lymphangiography and leakage resolution ranged from 8 to 13 days. There were neither complications of lymphangiography nor recurrence of lymphatic leakage in the successful cases. CONCLUSIONS: Intranodal lymphangiography may be not only a diagnostic tool but also an effective, minimally-invasive, and safe method for treatment of lymphatic leakage resistant to drainage after kidney transplantation.

Spontaneous ovarian tumors in domestic carp (Cyprinus carpio): light and electron microscopy.

Massive abdominal enlargement was discovered in 8 adult carp (Cyprinus carpio) 4-6 years old, living in breeding ponds of carp fisheries in northern Japan. The abdominal enlargements rapidly progressed and the affected fish died within a few months. At necropsy, single or multiple tumors up to 20 cm in diameter were found in the abdominal cavities. Ovarian tissue identified within the tumor capsule in 4 fish supported the impression, based on gross anatomic features, that the neoplasm arose in the ovaries. Histologically, the tumors were composed mainly of various types of mesenchymal cells. In one sample, striated muscle was identified by electron microscopy; in another, squamous cell nests were intermixed with mesenchymal elements. Although some tumors had areas of cellular pleomorphism suggesting a malignant character, no evidence of invasion or metastasis was found. These neoplasms were classified tentatively as dysontogenetic tumors of the ovary, possibly teratoid in nature.

[Primary biventricular repair for interrupted aortic arch with left ventricular outflow tract obstruction and tricuspid valve regurgitation; report of a case].

An interrupted aortic arch was diagnosed in a 10-day-old girl weighing 3.3 kg, as was perimembranous ventricular septal defect (VSD) and severe tricuspid valve regurgitation (TR). The subaortic diameter was 3.6 mm and the aortic valve (3.7 mm in diameter) was bicuspid. We chose definitive repair, modified Yasui procedure, because of severe TR and no straddling of mitral valve. In primary biventricular repair, we undertook extended aortic arch anastomosis. Left ventricular outflow tract reconstruction consisted of intracardiac rerouting from the VSD to the pulmonary artery by using expanded-polytetrafluoroethylene (ePTFE) and Damus-Kaye-Stansel (DKS) anastomosis. Right ventricular outflow tract reconstruction was performed by the Rastelli procedure with an ePTFE valved conduit. Moreover, we carried out semicircular annuloplasty for severe TR.

Clinical Experience of Late Conversion From Antimetabolites With Standard Exposure Calcineurin Inhibitors to Everolimus With Calcineurin Inhibitor Minimization in Stable Kidney Transplant Recipients With Good Renal Function.

INTRODUCTION: This study describes our clinical experience of late conversion from antimetabolites with standard exposure calcineurin inhibitors (CNIs) to everolimus with CNI minimization in stable kidney transplant recipients with good graft function. PATIENTS AND METHODS: A 1-year retrospective pilot study of 26 kidney recipients converted from antimetabolites with standard exposure CNIs to everolimus with CNI minimization was performed. The recipients enrolled in this study had normal or slightly impaired renal function defined as a serum creatinine value <2.0 mg/dL, and normal or slightly increased albuminuria defined as a urinary albumin excretion rate <100 mg/g creatinine. RESULTS: The median time from transplant to conversion was 39.5 months posttransplant (range, 3-275). Treatment with everolimus was stopped owing to adverse events in 11 patients (42.3%). In the analysis of the patients in whom everolimus was maintained, the mean estimated glomerular filtration rate (eGFR) significantly increased from 50.7 ± 11.9 mL/min/1.73 m(2) at baseline to 53.6 ± 13.9 mL/min/1.73 m(2) at 1 year after conversion. In the patients in whom everolimus was stopped during the observation period, there was no difference in eGFR between baseline and 1 year after conversion. CONCLUSIONS: This study demonstrated that, among the patients converted to everolimus at a late stage, there was no deterioration in renal function whether everolimus was maintained or stopped within 1 year after conversion.

Effects of Granulocyte and Monocyte Adsorptive Apheresis in Renal Transplantation Recipients With Concomitant Cytomegalovirus Infection.

BACKGROUND: Granulocyte and monocyte adsorptive apheresis (GMAA) is widely used as a treatment for active ulcerative colitis (UC) in Japan. Much attention has been paid to the possibility of GMAA for the treatment and control of cytomegalovirus (CMV) reactivation in patients with refractory UC and concomitant CMV infection. In this study, the effects of the combination of GMAA and antiviral therapy were examined in renal transplant recipients with concomitant CMV infection. METHODS: Combination therapy of GMAA and antiviral drugs was performed 9 times in 7 renal transplant recipients with concomitant CMV infection. Four of the cases were positive for CMV-IgG, and 3 were negative. The clinical presentation of CMV infection was viremia in 6 cases and disease (CMV retinitis) in 1 case. CMV infection was diagnosed by using an antigenemia assay (C7-HRP). GMAA session was performed once, and the duration of the session was 120 min. Immediately after the GMAA session, ganciclovir was administered at 5 mg/kg/body weight. CMV infection was monitored based on C7-HRP and CMV-DNA in the peripheral blood samples. RESULTS: All cases became negative for C7-HRP and CMV-DNA within 21 days (median, 14 days; range, 3-21 days) and 17 days (median, 6 days; range, 3-17 days), respectively, after starting the combination therapy. No side effects of GMAA were observed. CONCLUSIONS: This case series found that GMAA in combination with antiviral drugs may shorten the duration of treatment against CMV infection in renal transplant recipients. Further studies in a larger number of patients are required to confirm these results.

[Sandwich technique for closing of the large muscular Swiss-cheese type ventricular septal defects].

A 9-year-old girl, who has had a diagnosis as a Taussig-Bing anomary, underwent an original Jatene procedure (o-J) 2 months after birth. This time, she had a diagnosis of the muscular multiple ventricular septal defects (mVSD) and pulmonary stenosis after o-J. The mVSD was Swiss-cheese type and was large from the proximal of the infundibular septum to the apex and posterior of the septum. It was closed by the sandwich technique using a pair of felt patches, which of one was placed at right ventricular side and the other was at left ventricular side, slightly larger than the whole area of the mVSD. The patch fixation was placed with 1 stitch at the center between the patches and a few stitches around the right ventricular side patch to the ventricular septum. Postoperative cardiac function was uneventful regardless of the very large patches placed at the ventricular septum and the cardiac catheterization after 1 year postoperatively showed the pulmonary/systemic blood flow ratio was 1.0. This technique for the closure of the large Swiss-cheese type mVSD can be considered to be very effective.

Projections to the medial superior olive from the medial and lateral nuclei of the trapezoid body in rodents and bats.

In this study we present direct evidence of axonal projections from both the medial and lateral nuclei of the trapezoid body to the medial superior olive. Projections were traced by intracellularly labeling cells and axons in a tissue slice preparation of two rodent species, Mus musculus and Meriones unguiculatus and two bat species, Eptesicus fuscus and Pteronotus parnellii. The main axon of most principal cells in the medial nucleus of the trapezoid body gives off one or more collateral branches which arborize within the medial superior olive. These collateral axons form small bouton-like swellings which primarily contact somata within the central cell column in the medial superior olive. Likewise, labeled elongate and multipolar cells of the lateral nucleus of the trapezoid body send axons to both the medial and lateral superior olives. These axons also form perisomatic contacts in both target nuclei. These two sets of projections may relay ascending input to the medial superior olive and the lateral superior olive; the medial nucleus of the trapezoid body is known to relay input from the contralateral ventral cochlear nucleus, and the lateral nucleus of the trapezoid body may relay input from the ipsilateral ventral cochlear nucleus. These projections offer two routes for indirect, possibly inhibitory input to reach the medial superior olive from both cochlear nuclei. These indirect, inhibitory pathways may parallel the direct excitatory projections the medial superior olive receives from each cochlear nucleus.

Classification of the principal cells of the medial nucleus of the trapezoid body.

Cells in the medial nucleus of the trapezoid body were intracellularly labeled in brainstem tissue slices of two bat and two rodent species. The main cell type found in this nucleus, the principal cell, is an important link in the relay of ascending projections from the contralateral cochlear nucleus to the lateral superior olive, completing an essential pathway for sound localization. Principal cells are often viewed as a highly homogeneous group with a consistent morphology as well as a common function. Intracellular labeling has revealed a number of new axonal and dendritic features of principal cells. Some of these features vary widely from cell to cell, suggesting that the population of principal cells contains several morphologically distinct subgroups. Similar subsets of principal cells were recognized in all species examined. Five subgroups were distinguished on the basis of the position of dendritic fields. Although the dendrites of most labeled cells were confined to the medial nucleus of the trapezoid body, some principal cells had dendrites that spread outside the nucleus to one of several adjacent periolivary cell groups. Cells were also found that had dendrites that spread medially across the midline and into the contralateral medial nucleus of the trapezoid body. Axonal projections were used to distinguish two additional subgroups of principal cells. All principal cells project to the lateral superior olive and virtually all have one or more secondary projections. There are two subgroups with unusual collateral projections: one with collaterals that extended to the lateral lemniscus and one with recurrent collateral axons.

Afferents to the medial nucleus of the trapezoid body and their collateral projections.

Cells and axons that supply direct afferent input to the medial nucleus of the trapezoid body are described. Afferents were intracellularly labeled in brainstem tissue slices of two rodent and two bat species. The main afferents are calyciferous axons from globular bushy cells of the ventral cochlear nucleus. Calyciferous axons were highly consistent across species, projecting directly from the cochlear nucleus, across the midline in the trapezoid body, to the contralateral medial nucleus of the trapezoid body. Within the target nucleus, a typical axon turned sharply away from horizontal to form a large ending, the calyx of Held, around the soma of a single principal cell. Three groups of calyciferous axons were classified based on the path taken from bend to calyx. In subjects younger than four weeks, single axons often formed two calyces, each on a different cell. These calyx pairs were often found on adjacent or vertically aligned cells. In older animals, calyx pairs were more closely aligned, but fewer double calyx axons were seen. A secondary focus of this study was the system of thin collateral branches that characterizes calyciferous axons in all species. The projection patterns of these collaterals suggest that calyciferous axons may provide ascending input to periolivary cell groups with descending projections. In addition to calyciferous afferents, labeled cells that provide input to the medial nucleus of the trapezoid body from adjacent periolivary cell groups are described. Also described is a type of afferent that descends from the level of the lateral lemniscus to the medial nucleus of the trapezoid body.

Histopathologic studies of colorectal postendoscopic resection sites: "skipping electrothermal injury" associated with endoscopic resection procedures.

To elucidate the pathologic changes due to endoscopic resection (ER), 32 post-ER sites in 24 surgically removed colorectal specimens and the previous ER specimens were examined. The depth of all the previous ER specimens was restricted to the submucosa, and all post-ER sites showed submucosal stromal changes of various degrees. Fourteen sites (43.8%) showed muscular or serosal changes. One of these lesions was considered to be a reaction to a tattoo agent, but all the other lesions were considered to represent skipping electrothermal injury caused by electrical current passing through the colorectal wall. The lesions consisted of muscular depletion in the inner layer of the muscularis propria (12 sites, 37.5%), hemorrhage or fibrosis between the inner and outer layers of the muscularis propria (3 sites, 9.4%), and serosal changes (10 sites, 31.3%). These skip regions would be vulnerable to electrical current. These findings suggest that asymptomatic electrothermal injury associated with ER is frequent. Statistically, the electrothermal injury appeared to be related to the size of the previous ER specimens. However. these results also reveal that the ER of tissues <10 mm can cause electrothermal injury and can result in full-thickness necrosis.

Carcinogenic activity of 2-(2-furyl)-3-(5-nitro-2-furyl)-acrylamide, a food additive, in mice and rats.

The carcinogenicity of a food additive, 2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide (AF-2), was studied in Wistar rats and CDF1 mice. The rats developed mammary tumors; the first appearing 9 months after the start of the experiment. In mice fed AF-2 diet, squamous cell carcinoma of the forestomach was observed in the 11th month. Some mice had metastases in the liver, spleen, lymph nodes and peritoneal cavity.

Induction of colorectal adenocarcinoma in rats by amylopectin sulfate.

The carcinogenicity of orally administered amylopectin sulfate was studied in F344 rats. Amylopectin sulfate induced adenomas and adenocarcinomas in the rat colorectum. The incidences of tumor induction in groups that were given a 5% diet of amylopectin sulfate for 3, 6 and 9 months were 2 out of 20 rats (10%), 9 out of 20 rats (45%) and 12 out of 20 rats (60%), respectively. Squamous metaplasia of the colorectum persisted in all rats and progressed irreversibly. Amylopectin sulfate was deposited in the colorectal lamina propria, submucosa and regional lymph nodes. Amylopectin sulfate induced a lesion similar to that produced by degraded carrageenan in the rat colorectum.

A study on carcinogenesis induced by degraded carrageenan arising from squamous metaplasia of the rat colorectum.

We have undertaken studies on carcinogenesis arising from precancerous lesions, such as squamous metaplasia and ulcerative lesions of the rat colorectum, after termination of degraded carrageenan administration. Rates of tumor incidence in groups that were given a 10% diet of degraded carrageenan for 2, 6 and 9 months were 5 rats out of 39 (12.8%), 8 out of 42 (19.0%) and 17 out of 42 (40.5%), respectively. The colorectal squamous metaplasia persisted in all rats and progressed irreversibly. Degraded carrageenan was deposited not only in the colorectal propria mucosa, but also in the other reticuloendothelial organs. These results show that, even with short-term degraded carrageenan administration, degraded carrageenan is carcinogenic to the colorectum of the rat after a prolonged period.

The liver in systemic lupus erythematosus: pathologic analysis of 52 cases and review of Japanese Autopsy Registry Data.

We present pathologic findings for 52 livers (51 autopsy specimens and one wedge biopsy specimen) from patients with systemic lupus erythematosus (SLE). Hepatic congestion was the most common disease (40 livers), followed by fatty liver (38), arteritis (11), cholestasis (nine), peliosis hepatis (six), chronic persistent hepatitis (six), nonspecific reactive hepatitis (five), cholangiolitis (four), nodular regenerative hyperplasia of the liver (three), and hemangioma (three). The data obtained here suggest that arteritis of the SLE liver is more common than has been recognized previously. One patient had hepatic infarction complications induced by arteritis. On the basis of the findings in the present study and a review of the literature, we suggest that hepatic infarction resulting from arteritis is rare in SLE. On the other hand, while occurrence of nodular regenerative hyperplasia of the liver in SLE patients has been considered to be rare, our findings suggest that it may be more common than has been recognized previously. Although congestion and cholestasis may be acute terminal illnesses, fatty change is considered to be specific to the SLE liver. Statistical analysis indicates that exposure to a large dosage of glucocorticoids is a significant factor in the etiology of severe fatty liver. In addition, our review of Japanese autopsy registry data for 1,468 patients with SLE indicates that the incidence of chronic liver diseases in SLE autopsy cases is as follows: chronic hepatitis, 2.4%; cirrhosis, 1.1%; and liver fibrosis, 0.8%.

The lung in polyarteritis nodosa: a pathologic study of 10 cases.

Polyarteritis nodosa (PAN) is characterized by necrotizing arteritis of medium-sized and small arteries in various organs. Pulmonary artery involvement in PAN has been considered rare. Previously, it also has been thought that patients with PAN do not have interstitial pneumonitis and fibrosis. A detailed pathologic analysis of pulmonary diseases associated with PAN was made in 10 autopsy cases of PAN. Arteritis affecting bronchial arteries was present in seven patients (70%). The data obtained suggest that arteritis in the lung in patients with PAN is more common than has been recognized previously. Diffuse alveolar damage (DAD) involving all lobes bilaterally was present in five patients; it was acute in two patients and organizing in three. In the patients with organizing DAD the degree of fibrosis in the interstitium differed among the lobes, and the fibrosis was more severe in the lower lobe than in the other lobes. Two patients presented with interstitial fibrosis with honeycomb lung of the posterior and lateral basal segments of the lower lobes of both lungs; in one of these patients interstitial fibrosis was present in an area of organizing DAD. Five patients died of respiratory failure resulting from DAD. In conclusion, it is important to consider DAD and interstitial fibrosis as complications of PAN.

Geniculo-collicular descending projections in the gerbil.

Axonal projections were labeled using a combination of tract-tracing and intracellular staining to examine the connection between the auditory thalamus and tectum. We report descending projections from the medial and dorsal divisions of the medial geniculate body to the external nucleus of the ipsilateral inferior colliculus and lower brainstem of the gerbil. These were studied in quasi-parasagittal brain slice preparations containing auditory thalamus, tectum and brainstem. Slices were cut in a curved, roughly parasagittal plane from the level of the thalamus to the brainstem. When properly cut, a single thick slice included most of the ipsilateral auditory cell groups and pathways at these levels. The geniculo-collicular projections were revealed after extracellular injections of Biocytin and rhodamine-conjugated biotinylated dextran amine in the medial geniculate body were applied to these slices. Furthermore, cells in the medial geniculate body that had been retrogradely prelabeled with a fluorescent tracer, Fluoro-Gold, injected in the inferior colliculus were intracellularly labeled to confirm the presence of the descending axons. In these preparations, single cells with descending axons were traced through their entire extent to their terminals in the inferior colliculus. Our results clearly demonstrate the geniculo-collicular descending projection and suggest a thalamo-tectal feedback loop.

Local collateral projections from the medial superior olive to the superior paraolivary nucleus in the gerbil.

Local collateral projections from the medial superior olivary nucleus in the gerbil auditory brainstem were examined to study the possible communication of this nucleus with periolivary cell groups. The projections were investigated using intracellular and extracellular labeling with Biocytin in the medial superior olive (MSO) in brainstem tissue slices. Collateral axons were found to branch from the main axons of the central cells of the MSO as the latter passed through a dorsally neighboring periolivary nucleus, the superior paraolivary nucleus (SPN), toward the ipsilateral inferior colliculus (IC), their traditionally accepted target. Bouton-like endings and en passant varicosities of these collaterals appeared to contact the somata and proximal dendrites of cells within the SPN. Furthermore, close observation revealed that these collaterals terminate on at least two types of SPN cells. Intracellular labeling of the collateral axons of the MSO neurons combined with retrograde prelabeling of their target cells, however, revealed that the collaterals selectively contact the cells of the SPN that project to the ipsilateral IC. A link between the MSO and SPN has not been reported previously. This connection is of interest since SPN cells themselves project either to the cochlear nuclei (CN) or the IC. The MSO-SPN projection identified here raises the possibility that the latter may serve as an ancillary channel to convey MSO information to the IC.