Hashimoto's encephalopathy after interferon therapy for hepatitis C virus in adult liver transplant recipient accompanied by post-transplant lymphoproliferative disorder related to Epstein-Barr virus infection.

A 55-year-old woman underwent living-donor liver transplantation (LDLT). She had no history of autoimmune diseases. Spleen was preserved. Steroids were withdrawn at 3 months after LDLT. Epstein-Barr virus (EBV) infection occurred at 3.5 years after LDLT. Recurrent hepatitis C virus infection was confirmed at 4.5 years after LDLT, and pegylated interferon was introduced. Diagnosis of EBV-positive post-transplant lymphoproliferative disorder (PTLD) was made at 4.8 years after LDLT, and tacrolimus (Tac) was stopped completely. Then, unconsciousness, convulsion, and cervical stiffness appeared suddenly. Electroencephalography, cerebrospinal fluid analysis, and image studies revealed normal or only nonspecific findings. The patient was in a state of exhaustion; therefore, steroid pulse therapy (SPT) was attempted. Surprisingly, her general condition, including consciousness disturbance, was improved markedly, and Hashimoto's encephalopathy (HE) was suspected, based on this reaction to SPT. Elevations of anti-thyroglobulin antibody and anti-thyroid peroxidase antibody were confirmed. After withdrawal of Tac, and treatment with acyclovir and steroids, EBV-positive PTLD and HE improved, although they recurred at 5.1 years after LDLT. SPT improved only neurological symptoms. Molecular-targeted therapy was given for recurrent PTLD, based on analysis of sampling specimens. This therapy was effective, but tumor lysis syndrome occurred, and the patient died at 5.3 years after LDLT.

Giant cell reparative granuloma of the proximal tibia: a case report.

Giant cell reparative granulomas (GCRGs) are non-neoplastic inflammatory lesions, usually of the jaw or gingiva or small bones of the hands and feet. We report one such case in the right proximal tibia of a 45-year-old man. Radiological studies showed a lytic lesion with marginal sclerosis in the epiphysis and metaphysis. After open biopsy, a preliminary diagnosis of a benign giant cell tumour was made. One month after admission, the lesion was curetted and filled with cancellous bone and hydroxyapatite. Based on the histology of the curetted lesion, the diagnosis was changed to a GCRG. The patient had an uneventful postoperative course, with no evidence of local recurrence and metastasis. He died from gastric cancer 2 years later.

Vascular endothelial cells provide T cells with costimulatory signals via the OX40/gp34 system.

We investigated whether gp34, the ligand of OX40, expressed on EC is involved in costimulation of T cells. Normal CD4+ T cells were stimulated with anti-CD3-coated beads, phytohemagglutinin (PHA), or concanavalin A (Con A) in the presence or absence of irradiated human umbilical vein endothelial cells (HUVEC). Stimulation of T cells with each of these mitogens results in significant T-cell proliferation only when HUVEC were present, and this proliferation was inhibited markedly by anti-OX40 or anti-gp34 monoclonal antibody (mAb). T cells cultured with HUVEC produced more interleukin (IL)-2 than those cultured without HUVEC. The addition of anti-IL-2R alpha chain and anti-IL-2R beta chain mAbs abolished the costimulatory effects of HUVEC. Thus, the augmentation of T-cell proliferation appears to be attributable to increased IL-2 production. These results suggest that gp34 expressed on HUVEC plays a role in potentiation of T-cell immune response by providing OX40+ T cells with costimulatory signals.

[Successful repair of supravalvular aortic stenosis using Steinberg 3 sinuses reconstruction; report of a case].

Steinberg method is a modification of Doty extended aortoplasty for supravalvular aortic stenosis (SAS). This modification entails placement of an additional patch in the left coronary sinus. A 3-year-old boy was diagnosed as SAS with aortic valvular stenosis. He was noticed a systolic murmur from 1 month after his birth. Echocardiography showed left ventricular hypertrophy, and pressure gradient of 80 mmHg was measured between the ascending aorta and the left ventricle. Cardiac catheterization revealed severe aortic stenosis at the sino-tubular (ST) junction. We adopted Steinberg 3 sinuses reconstruction. After this operation, there was no pressure gradient at ST junction although aortic valvular stenosis remained and mild aortic valve regurgitation newly developed. As this method can produce a symmetric aortic root, it may reduce aortic valve deformity especially on the left coronary cusp.

Responsiveness of monkey preoptic thermosensitive neurons to non-thermal emotional stimuli.

Responsiveness of 143 preoptic neurons to changes in hypothalamic temperature and to non-thermal emotional stimuli were investigated while rewarding (foods) and aversive objects (hypertonic saline, a toy snake, an air puffer) were given. About 71% of thermosensitive neurons and 32% of thermally insensitive neurons changed the activity when emotional stimuli were shown to and/or tasted by the monkey. Such responses were modulated by satiety/hunger state and were dependent on the degree of perturbation of emotional state. About half of the neurons tested responded when the monkey opened the mouth and protruded the tongue or moved fingers in trying to obtain foods with strong motivation, but did not when the animal made such movements less readily or reluctantly with the progress of satiation. This response was most frequently found among warm-units. The results raise a possibility that preoptic thermosensitive neurons, besides their postulated thermoregulatory functions, might be involved in the response of coordination with thermal and non-thermal emotional behaviors controlled in the hypothalamus.

Patent foramen ovale as a possible risk factor for cryptogenic brain abscess: report of two cases.

OBJECTIVE AND IMPORTANCE: Patent foramen ovale (PFO) has been suggested as a potential source of paradoxical embolism. A higher prevalence of PFO in ischemic stroke of unexplained cause has been recognized. Brain abscesses are commonly associated with a contiguous focus of infection, hematogenous spread from a distant focus, or cranial trauma. However, no predisposing factors, including a distant focus with unknown cause, are identified in approximately 15 to 30% of reported cases. CLINICAL PRESENTATION: We encountered two patients with brain abscess presumably caused by dental infections. Both patients displayed PFO, through which right-to-left atrial contrast shunting was revealed by transesophageal echocardiography. Although the radiological location of the abscesses suggested hematogenous spread as a cause, the patients had no arteriovenous shunting other than the PFO, despite exhaustive investigations for a potential infectious route. The patients displayed no definite focal orofacial inflammatory signs during the postoperative course despite diagnosis of pyorrhea alveolaris or periodontitis. INTERVENTION: In Patient 1, the abscess was aspirated stereotactically, and in Patient 2, the abscess disappeared radiologically after high-dose antibiotic treatment. CONCLUSION: The mechanism of brain abscess formation putatively related to PFO should be different from that related to common dental sepsis. Analysis of these cases suggested that infectious embolism from a latent or even identifiable focus through the PFO may be an underrecognized cause of brain abscess, in contrast to simple seeding of the brain via transit of the infecting bacteria through the valveless emissary veins.

Presence of Streptococcus infection in extra-oropharyngeal head and neck squamous cell carcinoma and its implication in carcinogenesis.

To investigate the involvement of S. anginosus infection in head and neck cancer in the extra-oropharyngeal cavity, we analyzed 3 DNA samples prepared from squamous cell carcinoma of the external auditory canal and one from squamous cell carcinoma of the skin using polymerase chain reaction (PCR) analysis and Southern blot analysis to detect the DNA sequence of S. anginosus. We also examined these four specimens by Gram's stain to detect the streptococcal bacterial bodies. By PCR analysis, the DNA sequence of S. anginosus was found in 4 out of 4 (100%) DNA samples obtained from these tumors. By Southern blot analysis, positive bands were detected in one out of the 3 (33%) samples from the tumor taken from the external auditory canal. We detected streptococcal bacterial bodies in one of the three specimens from the tumor obtained from cancer of the external auditory canal and in the one specimen from the skin cancer by the method of Gram's stain. Contrary to our expectations, these bacterial bodies were located in the middle of the tumor. Since S. anginosus is thought to exist in the mouth as a normal flora and to be located mainly in the gingiva and dental plaque, these data strongly indicate that S. anginosus infection is implicated in the carcinogenesis of head and neck squamous cell carcinoma.

Streptococcus anginosus in head and neck squamous cell carcinoma: implication in carcinogenesis.

It has been suggested that Helicobacter pylori (H. pylori) infection might be associated with not only gastric ulcers but also gastric malignancies. Recently, it was reported that the Streptococcus anginosus (S. anginosus) DNA sequence was found in DNA samples extracted from esophageal cancers. Because smoking and alcohol abuse are regarded as risk factors for both esophgeal cancer and head and neck cancer, infection of S. anginosus might be associated with carcinogenesis of head and neck cancer. To investgate the involvement of S. anginosus infection in head and neck cancer, we analyzed 217 DNA samples prepared from head and neck squamous cell carcinomas. We performed PCR analysis with S. anginosus-16S ribosomal DNA-specific primers, and Southern blot analysis. For detection of S. anginosus in the oral and pharyngeal cavities, we used oropharyngeal bacteriological culture and PCR analysis of gingival smears of the patients. By PCR analysis, the S. anginosus DNA sequence was found in 217 out of 217 (100%) DNA samples obtained from head and neck cancers. By Southern blot analysis, positive bands were detected in 41 out of 125 (33%) samples. We could find no S. anginosus colony in oropharyngeal bacteriological culture dishes of 53 patients with and without head and neck cancer. On the other hand, we found the S. anginosus DNA fragment in 8 out of 8 DNA samples obtained from gingival smears by PCR analysis. These data indicate that the upper aerodigestive environment of the patients permitting S. anginosus infection was implicated in the carcinogenesis of head and neck squamous cell carcinoma.

The effect of various concentrations of collagen barrier on periodontal wound healing.

Collagen membrane preparations were manufactured with the aim of enhancing wound healing following periodontal surgery. In order to clarify effects of different concentrations of collagen on wound healing, a basic study was performed. Solutions containing 0.5%, 1.0%, and 1.3% atelocollagen were treated with hexamethylenediisocyanate (HMDIC) for cross-linking, and collagen membranes were prepared with each solution. Periodontal flap surgery was performed on the palatal gingiva beside the maxillary first molar teeth in rats. The root surface of the tooth was exposed and curretted. Then, a piece of atelocollagen membrane was implanted. The healing of the wound was studied histologically and the following findings were made. (1) Apical migration of the junctional epithelium occurred within 2 weeks postoperatively. (2) The implantation of atelocollagen membrane significantly reduced the apical migration. (3) The apical migration of the epithelium did not vary with collagen concentration.

Aspartate aminotransferase (AST) levels in human periodontium-derived cells.

The ability to objectively assess periodontal disease activity can significantly affect periodontal therapy. Aspartate aminotransferase (AST) is released extracellularly upon tissue destruction which suggests its potential as a key index in a quantitative assay for evaluating periodontal disease activity. The purpose of the present research was to assess the origin of AST in gingival crevicular fluid (GCF) in vitro. An experimental kit was used for the measurement of AST level in human gingival epithelial cells (HGEs), human gingival fibroblasts (HGFs), human periodontal ligament fibroblasts (HPLFs), polymorphonuclear leukocytes (PMNs), and plasma in peripheral blood. AST activity levels were observed in all of the periodontally derived cells, PMNs, and plasma. A significantly high level of AST activity was observed in HGEs (104.93 +/- 8.13 KU/1000 cells). The level of AST activity in HPLFs was 18.09 +/- 3.73 KU/1000 cells. AST activity in PMNs was significantly low, approximately 2% of that observed in HPLFs. These findings may suggest that AST level in GCF is correlated with the destruction of periodontal tissue.

Subgingival administration of tetracycline on a collagen film.

The purpose of this study was to evaluate the duration of therapeutic effect after administration of the collagen film immobilized tetracycline (TC film). TC film or tetracycline non-immobilized placebo film was applied one time to the periodontal pocket (greater than or equal to 4 mm) of five periodontitis patients (20 teeth). The clinical and microbiological effects are summarized as follows: The group that received TC film continued to show significantly low values for bleeding upon probing the pocket depth for 3 and 4 weeks, respectively, after administration, but there was no significant difference in the plaque index or gingival index when compared with the group that received a placebo film. In the TC film group, the density of microorganisms and the proportion of motile rods and spirochetes were also significantly decreased 3 weeks after administration. These findings suggest that topically administered TC film remains both clinically and bacteriologically effective for 2 to 3 weeks.

Histological study of the hydroxyapatite-collagen complex implants in periodontal osseous defects in dogs.

This study was performed to determine whether the process of wound healing, following periodontal surgery, could be improved through the combined use of collagen and grafting of hydroxyapatite (HAP) particles. Twenty-four proximal defects were made in the mandibular fourth premolars and second molars of six adult mongrel dogs. Steel wires and resin were put into the defect to enhance plaque formation. At eight weeks, the wires and resin were removed. At ten weeks, HAP or HAP-collagen complex was implanted during reconstructive surgery, along the root surface treated with acid conditioning. Dogs that received no implant following a flap operation served as controls. In these three groups of animals, differences in the extent and features of healing were histopathologically examined two months later. Animals implanted with a HAP-collagen complex showed a larger amount of new cementum formation when compared with HAP-implanted or control animals. In addition, in animals from the HAP-complex group, the interdigitation between the root surface and the gingival connective tissue fibers tended to be reinforced resulting in suppressed epithelial downgrowth. However, neither bone formation nor the reformation of the periodontium was promoted in the HAP-collagen complex group. These results suggest that implantation of an HAP-collagen complex promotes cemento-genesis of the demineralized root surface and can establish a stronger interdigitation between the root surface and the gingival connective tissue fibers.

Application of a local drug delivery system to periodontal therapy: I. Development of collagen preparations with immobilized tetracycline.

For the purpose of applying a local drug delivery system to periodontal therapy, atelocollagen preparations with immobilized tetracycline (TC) were prepared by modifying the form of the collagen, the concentration of the immobilized TC, and the time of the cross-link process with glutaraldehyde. The course of the TC release from the collagen preparations into an aqueous solution was determined in relation to time. The preparations were also inserted into periodontal pockets, and the amount of TC remaining in the pocket was determined daily. The results obtained were as follows: 1) The degree of drug release could be controlled to some extent by adjusting the TC concentration and the time of the cross-link process; and 2) an amount of TC exceeding the effective dose in the gingival crevicular fluid was present in the periodontal pocket even 10 days after the insertion of TC fixed in the cross-linked processed collagen film in the periodontal pockets.

Different cross-linked types of collagen implanted in rat palatal gingiva.

Collagen membrane preparations were manufactured with the aim of enhancing wound healing following periodontal surgery. After crosslinking by various processing methods (with ultraviolet and hexamethylenediisocyanate) and to various extents, two types of collagen (atelocollagen and tendon collagen) were implanted into a dissection site within palatal gingival tissue. The time course of healing responses was investigated histologically. Collagen implantation was found to accelerate fibrous connective tissue attachment to the root surface and inhibit apical migration of the junctional epithelium. Cross-linked atelocollagen was superior in biocompatibility to the other collagen membranes studied.

Effect of mechanical stimulation by tooth brushing on oxygen tension in dog gingiva.

To determine oxygen tension (pO2) in gingival tissue, an oxygen micro-electrode with a membrane-coated Pt needle was inserted into the gingiva of 12 dogs. Teeth were brushed using a modified Bass technique for 10 s under 200 g pressure. pO2 increased and reached a maximum 15 min after brushing, then gradually returned to the baseline. A significant increase in pO2 persisted for approx. 1 h. These findings suggest that short-term stimulation by tooth brushing increases oxygen tension in the gingiva.

[A mechanism of cheiro-oral syndrome due to brainstem lesions, a case of a dissecting aneurysm of the basilar artery].

A 42-year-old woman developed an abrupt onset of severe headache, nausea, vomiting, unstable gait and numbness around the right side of her mouth and in her right hand. Neurological examination revealed bilateral pyramidal tract signs and hypesthesia of her right palmar tip and the right side of her mouth. However, pain and temperature sensibility was preserved. Cerebrospinal fluid was clear and colorless. CT scan showed an enhancing mass in the prepontine cistern compressing the pontine base. Vertebral angiography revealed irregular narrowing of bilateral vertebral arteries (string sign) proximal to a fusiform aneurysm on the entire length of the basilar artery. MRI showed double lumina in the wall of the aneurysm. The medial lemniscus conducts the discriminatory tactile and the deep sensory impulses from the extremities. The ventral ascending tract of the trigeminal nerve conducts the discriminatory tactile sensory impulses from the face. These two tracts lie close together in the pontine tegmentum, which is also a watershed area of the paramedian branches and circumferential branches of the basilar artery. We suggest that in this case the dissecting aneurysm caused ischemia of these two tracts in the left pontine tegmentum, presenting right cheiro-oral syndrome.

Giant negative T waves after maxillofacial surgery.

A patient developed strongly negative T waves following anesthesia for maxillofacial surgery. The electrocardiogram was normal preoperatively, except for a single premature ventricular depolarization, and no abnormalities were noted during the operation. Postoperatively, the T wave gradually inverted in almost all leads and approached the criterion of -10 mm for giant negative T waves in V3 2 days postoperatively. The T wave returned to normal approximately 4 months later. Although the T-wave inversion in this patient may have been caused by surgical trauma to the sympathetic nerve supply to the heart or by myocardial infarction, the exact cause remains undetermined.

An echocardiographic study of interactions between pindolol and epinephrine contained in a local anesthetic solution.

An increasing number of dental patients are taking beta-adrenergic blockers for the treatment of hypertension or angina pectoris. If epinephrine-containing local anesthetics are administered to such patients, interactions between epinephrine and the beta-blocking agent may induce cardiovascular complications. We assessed in volunteers the effects of intraoral injection with 2% lidocaine containing 1:80,000 epinephrine (L-E) on cardiac function after pretreatment with the beta-blocking agent pindolol. M-Mode echocardiography was used for the assessment. The injection of L-E after administration of pindolol did not alter cardiac preload, whereas it reduced the stroke volume, due to an increase in afterload and a decrease in myocardial contractility. Reductions in stroke volume and heart rate led to a decrease in cardiac output. Because total peripheral vascular resistance increased markedly, blood pressure was elevated despite the reduced cardiac output. These results suggest that cardiac function of dental patients on beta-blocker therapy can be adversely affected by epinephrine-containing local anesthetics. Therefore, when such an anesthetic solution has to be used in patients on beta-blocker therapy, careful systemic monitoring is needed.

The interaction between pindolol and epinephrine contained in local anesthetic solution to the left ventricular diastolic filling velocity in normal subjects.

To evaluate the interaction between the nonselective beta-blocker, pindolol, and epinephrine contained in a local anesthetic solution, the left ventricular diastolic filling velocity was examined with pulsed Doppler echocardiography. Arterial blood pressure (BP), the R-R interval on the electrocardiogram (RR), and Doppler echo-cardiographic measurements were recorded in seven healthy volunteers after 45 micrograms of epinephrine contained in lidocaine (L-E) was injected in the maxilla after pretreatment with 5 mg of pindolol. The administration of L-E caused the elevation of BP and an increase in RR interval. Peak early (E) and peak atrial (A) filling velocities decreased, whereas isovolumic relaxation time (IVRT) and diastolic filling period (DFP) were prolonged. Although the ratio of E to A (E/A) remained unchanged, E/A/DFP was reduced. In contrast, when L-E was given without pindolol pretreatment, RR interval was shortened and BP was unchanged. The increase of both E and A velocities and the shortening of both IVRT and DFP were observed. E/A remained unchanged but E/A/DFP was increased. These results suggested that L-E caused opposite effects on the left ventricular filling velocity in the presence or absence of pindolol. We conclude that epinephrine activates the left ventricular relaxation rate but impairs it in the presence of pindolol.

The effects of epinephrine and norepinephrine administered during local anesthesia on left ventricular diastolic function.

To evaluate the effects of epinephrine (E) and norepinephrine (NE) administered during local anesthesia on left ventricular diastolic function, we examined transmitral inflow patterns with pulsed Doppler echocardiography. Arterial blood pressure, heart rate, and transmitral inflow patterns were measured in 10 healthy volunteers when 3.6 mL of 2% lidocaine containing 1:80,000 E or 1:25,000 NE was injected supraperiosteally in the maxilla. The dosage of drug administered was 45 micrograms for E and 144 micrograms for NE. After the administration of E, heart rate was increased, but blood pressure was unchanged. Peak early velocity (R), peak atrial velocity (A), the ratio of A to R (A/R), and the deceleration rate (Dc) were increased, whereas the isovolumic relaxation time (IVRT) was shortened. The increase of R and Dc and the shortening of IVRT indicated an activation of left ventricular relaxation. After the administration of NE, blood pressure was increased and heart rate was decreased. A decrease in Dc, shortening of the acceleration half-time (AcT), and prolongation of IVRT were observed. These changes reflect impeded myocardial relaxation. We conclude that E activates left ventricular diastolic function and that NE, in contrast, impairs it.