An elderly case of paraneoplastic anti-NMDA receptor encephalitis associated with large cell neuroendocrine carcinoma of the lung.

BACKGROUND: Recent studies have suggested that N-methyl-D-aspartate (NMDA) receptors are involved in the cell proliferation in several tumors. However, there have been no reports demonstrating the expression of NR1 subunit of the NMDA receptor in large cell neuroendocrine carcinoma (LCNEC). CASE PRESENTATION: Here, we report the first elderly case of paraneoplastic anti-NMDA receptor encephalitis associated with LCNEC of the lung with NR1 expression. Of note, NR1 subunit expression in the tumor cells of the present case was confirmed by immunohistochemistry (IHC). Radiation therapy and immunotherapies, such as corticosteroids and intravenous immunoglobulin (IVIG), shrank the tumors and improved neurological symptoms in the present case. Additionally, we also confirmed the expression of NR1 in the tumor cells obtained from three other cases with LCNEC of the lung at our hospital by IHC. CONCLUSION: Our IHC results indicate that LCNEC generally expresses NR1 subunit and NMDA receptor may be involved in the tumor development and growth.

Factors Influencing Craniospinal Relapse of Intracranial Germinoma After Complete Remission.

OBJECTIVE: To evaluate the pathomechanism of the recurrence of intracranial germinoma after complete response and to confirm the association of the initial magnetic resonance imaging and therapeutic factors with recurrence. METHODS: This study included patients who were followed up for ≥5 years and who were treated in our hospital from 1980 to 2021. Those with germinoma and germinoma with syncytiotrophoblastic giant cells were diagnosed pathologically. Data were categorizedbased on "gender," "single region," "intraventricular dissemination at the initial diagnosis," "hydrocephalus," "types of radiation therapy (RT)," and "chemotherapy." Fisher's exact probability test was used to assess differences between the no recurrence and recurrence groups. RESULTS: Among 43 patients, 34 had no recurrence, 5 had delayed recurrence (≥60 months), and 4 had early recurrence (<60 months). Follow-up periods were 143.5 (60-380), 198 (88-222), and 132.5 (75-291) months for the no recurrence, delayed recurrence, and early recurrence groups, respectively. Five patients with delayed recurrence showed 3 intracranial lesions and 2 spinal lesions. Four patients with early recurrence showed 3 intracranial lesions and 1 spinal lesion. Differences in delayed recurrences (focal RT vs. RT including whole-ventricle system; P = 0.0491) were significant in Fisher's exact test. CONCLUSIONS: RT including the whole-ventricle system reduces delayed craniospinal relapses including dissemination, local, and distant recurrences even ≥5 years after complete response in patients with primary central nervous system germinoma.

Emergent carotid artery stenting for cervical internal carotid artery injury during carotid endarterectomy: A case report.

BACKGROUND: Carotid endarterectomy (CEA) has been the standard preventive procedure for cerebral infarction due to cervical internal carotid artery stenosis, and internal shunt insertion during CEA is widely accepted. However, troubleshooting knowledge is essential because potentially life-threatening complications can occur. Herein, we report a case of cervical internal carotid artery injury caused by the insertion of a shunt device during CEA. CASE DESCRIPTION: A 78-year-old man with a history of hypertension, diabetes, and hyperuricemia developed temporary left hemiplegia. A former physician had diagnosed the patient with a transient cerebral ischemic attack. The patient's medical history was significant for the right internal carotid artery stenosis, which was severe due to a vulnerable plaque. We performed CEA to remove the plaque; however, there was active bleeding in the distal carotid artery of the cervical region after we removed the shunt tube. Hemostasis was achieved through compression using a cotton piece. Intraoperative digital subtraction angiography (DSA) revealed severe stenosis at the internal carotid artery distal to the injury site due to hematoma compression. The patient underwent urgent carotid artery stenting and had two carotid artery stents superimposed on the injury site. On DSA, extravascular pooling of contrast media decreased on postoperative day (POD) 1 and then disappeared on POD 14. The patient was discharged home without sequela on POD 21. CONCLUSION: In the case of cervical internal carotid artery injury during CEA, hemostasis can be achieved by superimposing a carotid artery stent on the injury site, which is considered an acceptable troubleshooting technique.

[A Japanese case of melioidosis presenting as multiple organ lesions accompanied by sepsis and disseminated intravascular coagulation, after a visit to Thailand].

A 65-year-old man with diabetes mellitus reporting fever and urination disturbance on a flight from Bangkok back to Japan in July 2003 was admitted elsewhere for acute prostatitis. Despite intravenous antibiotics, his condition deteriorated. On admission to our hospital, he suffered from respiratory failure, with laboratory data showing disseminated intravascular coagulation (DIC). Computed tomography (CT) shows infiltrative and nodular shadows in both lung fields and low-density areas in the left kidney and prostate gland, consistent with pneumonia and abscesses in these organs. He also developed broad osteomyelitis in the right lower extremity with cellulitis and arthritis in the right hand, knee, and foot. Blood, urine, and joint fluid culture all yielded Burkholderia pseudomallei, so he was diagnosed with melioidosis. Treatment was started with meropenem and minocycline, then meropenem was changed to imipenem. His symptoms gradually improved after ciprofloxacin was added, so all intravenous antibiotics were discontinued and he underwent oral treatment with chloramphenicol, minocycline, and sulfamethoxazole/trimethoprim in September 2003. He developed fever again, however, and oral therapy was discontinued and intravenous antibiotics restarted. After resolution of fever, oral maintenance therapy was initiated again with levofloxacin and minocycline in October, and his condition remained stable. After discharge in April 2004, he has been followed up with no evidence of relapse. This is considered to be the seventh case of melioidosis reported in Japan. Our patient manifested multiple organ lesions with sepsis and DIC, and was difficult to treat, but clinical symptoms improved in long-term antibiotic administration. With travelers to Southeast Asia increasing, greater attention must be paid to imported infectious diseases, such as melioidosis.

Necrotizing arteritis occurring in an intralobar pulmonary sequestration of a patient without systemic vasculitis syndrome.

Necrotizing arteritis is a complex lesion of pulmonary hypertension, as are plexiform lesions, and is classically recognized as grade 6 in the Heath and Edwards grading scheme for hypertensive pulmonary vascular disease. The vascular changes observed in intralobar pulmonary sequestration have been reported to be similar to those observed in pulmonary hypertension, such as plexiform lesions. However, necrotizing arteritis occurring in an intralobar sequestration of a patient without systemic vasculitis syndrome has never been reported to our knowledge. Here, we report a case of a 38-year-old woman with pulmonary sequestration detected on a medical checkup. She was treated with surgery, and subsequent pathological analyses revealed necrotizing vasculitis in her sequestrated lung. We suspected systemic vasculitis syndromes, such as Takayasu arteritis, polyarteritis nodosa, and antineutrophil cytoplasmic antibody-associated vasculitis. However, physical and blood examination did not show any other abnormalities, and hence, she did not have systemic vasculitis syndrome. Immunohistochemical analyses of the resected specimen showed that inflammatory cells of the arteries were mainly composed of T lymphocytes. T-lymphocytic inflammation with little neutrophil and histiocyte infiltration may be a pathological feature of necrotizing arteritis observed in pulmonary sequestration. This is the first case to our knowledge of necrotizing arteritis in an intralobar pulmonary sequestration of a patient without systemic vasculitis syndrome.

Solitary Pulmonary Capillary Hemangioma of Adult Cases: Clinicopathologic Characteristics as an Unrecognized Entity.

Solitary pulmonary capillary hemangioma (SPCH) is a rare disease, first described about autopsy cases in 2000 and about surgically resected cases in 2006. To date, only 9 surgically resected cases have been published in English. Here, we report 7 original cases with surgery (median age, 54 y; 4 females, 2 never-smokers). All patients were asymptomatic, and all nodules were detected by computed tomography (CT). The median (range) size of nodule was 11 (8 to 16) mm. Six of 7 cases showed the part-solid nodule appearance and 1 showed pure ground-glass nodule appearance in CT findings. The growth speed was very slow. No abnormal uptake of fluorine-18 fluorodeoxyglucose was observed in systemic positron-emission CT in all 3 cases we examined. No patients died from SPCH. Histologically, SPCH manifested as a solitary lesion composed of densely proliferating and dilated capillaries without cytologic atypia within the alveolar septa. In addition, capillaries of SPCH spread into the vascular lumen and involved the walls of bronchioles with protrusion into the lumen. Immunohistochemically, capillaries of SPCH uniformly expressed endothelial markers, such as CD31, CD34, and Factor VIII; and α-smooth muscle actin positive cells were also observed. To be accurately diagnosed, especially in intraoperative frozen sections, SPCH should be conceived as an entity that presents as a solitary nodule in CT. We propose that SPCH is an unrecognized benign capillary proliferative disease.

Lung adenocarcinoma associated with familial adenomatous polyposis. Clear cell carcinoma with beta-catenin accumulation accompanied by atypical adenomatous hyperplasia.

A 46-year-old man presented with a lung tumor 17 years after a subtotal colectomy and 13 years after a partial duodenectomy for familial adenomatous polyposis (FAP). There had been no malignant transformation in the specimens from his colectomy and duodenectomy, and a current gastrointestinal investigation revealed no evidence of malignancy. Pathological analysis of the lung tumor demonstrated adenocarcinoma with clear cells and a papillary structure, accompanied by tiny tumorous nodules in the background lung parenchyma. Many of the nodules were multifocal adenocarcinoma; however, some of the nodules demonstrated atypical adenomatous hyperplasia (AAH). This is the first case report of a lung adenocarcinoma accompanied by AAH in a FAP patient. Immunohistochemical and loss of heterozygosity studies revealed unique features of the lesions reflecting a disruption of the adenomatous poliposis coli-beta-catenin pathway.

Voltage-gated sodium channel expressed in cultured human smooth muscle cells: involvement of SCN9A.

Voltage-gated Na(+) channel (I(Na)) is expressed under culture conditions in human smooth muscle cells (hSMCs) such as coronary myocytes. The aim of this study is to clarify the physiological, pharmacological and molecular characteristics of I(Na) expressed in cultured hSMCs obtained from bronchus, main pulmonary and coronary artery. I(Na), was recorded in these hSMCs and inhibited by tetrodotoxin (TTX) with an IC(50) value of approximately 10 nM. Reverse transcriptase/polymerase chain reaction (RT-PCR) analysis of mRNA showed the prominent expression of transcripts for SCN9A, which was consistent with the results of real-time quantitative RT-PCR. These results provide novel evidence that TTX-sensitive Na(+) channel expressed in cultured hSMCs is mainly composed of Na(v)1.7.

Design of attachment type of drug delivery system by complex formation of avidin with biotinyl drug model and biotinyl saccharide.

Recent studies have focused on the active targeting of drug delivery by combining a homing device and antitumor drug. For this purpose, synthesis of a well-designed vehicle (such as polymer/drug conjugates or nanoparticles) carrying a drug and a homing device requires many steps. We propose a new type of drug delivery system (DDS) by formation of a complex containing avidin (Av) plus biotinyl drug with a biotinyl homing device, which easily accommodates the combination of various drugs and homing devices. The targetable drug complex can be prepared by selecting an appropriate biotinyl drug derivative and a biotinyl homing device and mixing them with avidin. Fluorescent dye with 5-(and-6)-carboxytetramethylrhodamine (TAMRA) was used as a drug model, and galactose (Gal) recognized by liver parenchymal cells was used as a homing device. TAMRA and galactose were attached to biotin (Bio) through a triethyleneglycol (TEG) spacer group to give Bio-TEG-TAMRA conjugate and Bio-TEG-Gal conjugate, respectively. Confocal laser scanning microscopic studies suggest that the complexes prepared by mixing Bio-TEG-Gal conjugate and fluorescein isothiocyanate (FITC)-labeled Av (feed molar ratio 4:1), and mixing Bio-TEG-Gal conjugate, Bio-TEG-TAMRA conjugate and FITC-labeled Av are internalized into the hepatoma cells through a receptor-mediated endocytosis mechanism.

Oxygenation abnormalities in normoxemic patients with mild liver cirrhosis.

OBJECTIVE: Nitric oxide (NO) production is enhanced in patients with liver cirrhosis (LC). Although most patients with mild LC have neither dyspnea nor platypnea, they might have mild oxygenation abnormalities due to intrapulmonary vasodilatation caused by increased NO. We investigated whether oxygenation abnormalities, such as hypoxemia and orthodeoxia, are present in patients with mild LC. METHODS: We investigated 148 consecutive patients with biopsy-proven chronic liver diseases such as CH (noncirrhotic chronic hepatitis) (n=46), LC(A), LC(B), and LC(C) (LC Child's A, B, and C) (n=18, 51, 33, respectively). The oxygen saturation by pulse oximetry (SpO2) in the supine and upright positions was determined in patients and controls (normal subjects, n=29). The change in SpO2 on standing was defined as deltaSpO2. NO output in exhaled air was measured in 16 patients. RESULTS: Four patients [two LC(B) and two LC(C)] had hypoxemia (supine SpO2< or =94% and/or upright SpO2< or =94%). Although there was no intergroup difference in the supine SpO2 or the upright SpO2, the deltaSpO2 decreased [control, +0.2+/-0.6%; CH, +0.1+/-0.9%; LC(A), -0.3+/-0.8%; LC(B), -0.2+/-0.9%; LC(C), -0.5+/-1.1%; mean+/-SD; p=0.005] with worsening liver disease, and the prevalence of desaturation on standing (deltaSpO2< or =-1%) increased [control, 7%; CH, 20%; LC(A), 33%; LC(B), 35%; LC(C), 42%; p=0.01]. The NO output was inversely correlated with deltaSpO2 (r=-0.66, p=0.006). CONCLUSIONS: Desaturation on standing is present in one-third of normoxemic patients with mild LC of Child's A, and is associated with the severity of liver disease. This postural desaturation is correlated with the exhaled NO, which suggests that intrapulmonary vasodilatation may play some role in this phenomenon.

Microscopic polyangiitis accompanied by pleuritis as the only pulmonary manifestation of occupational silica exposure.

A 68-year-old man, who had worked for processing quartz-containing stones for more than 50 years, complained of low-grade fever and arthralgia. Mediastinal lymph nodes were markedly swollen on chest computed tomography. Pathological findings of the lymph node were compatible with silicosis, with a high titer of myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA). During follow-up with prednisolone treatment, pleuritis and uveitis developed as manifestations of vasculitis. Thus, he was diagnosed with MPO-ANCA-associated vasculitis with occupational silica exposure, possibly microscopic polyangiitis (MPA). This case is rare, because pleuritis was the only pulmonary manifestation, without interstitial pneumonia, alveolar hemorrhage or glomerulonephritis.

Mucosa associated lymphoid tissue (MALT) lymphoma of the thymus with trisomy 18.

Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) of the thymus is rare and little is known about its karyotype abnormality. MALT lymphoma in general shows a good prognosis, but some reports suggest that the presence of trisomy 18 predicts recurrence. Here, we report a patient with MALT lymphoma of the thymus and the left parotid gland accompanied by Sjogren's syndrome. The karyotype analysis revealed that this is the first case of thymic MALT lymphoma with trisomy 18, which we believe is worth reporting. We also review cases with thymic MALT lymphoma previously reported in the literature.

An adult case of multiple squamous papillomas of the trachea associated with human papilloma virus type 6.

A 72-year-old woman with primary biliary cirrhosis complained of dry cough and wheezing. Chest computed tomography showed a tumor arising from the posterior wall of the trachea. Bronchoscopic examination revealed that the tumor was cauliflower-like, with two small polypoid tumors. They were diagnosed as multiple squamous papillomas. The main tumor was recurrent and removed by repeated microwave coagulation therapy (MCT) through bronchoscopy, whereas the two polypoid tumors were likely to disappear spontaneously. Human papilloma virus (HPV) type 6 DNA was detected in the tumor by polymerase chain reaction (PCR) amplification, suggesting that this virus was the cause of her papillomas.

Manipulabilities of the index finger and thumb in three tip-pinch postures.

Tip-pinch, in which the tips of the index finger and thumb pick up and hold a very fine object, plays an important role in the function of the hand. The objective of this study was to investigate how human subjects affect manipulabilities of the tips of the index finger and thumb within the flexion/extension plane of the finger in three different tip-pinch postures. The index finger and thumb of twenty male subjects, were modeled as linkages, based on measurement results obtained using two three-dimensional position measurement devices. The manipulabilities of the index finger and thumb were investigated in three tip-pinch postures, using three criteria indicating the form and posture of the manipulability ellipse of the linkage model. There were no significant differences (p > 0.05, ANOVA) in each criterion of each digit across the subjects, except for two criteria of the thumb. The manipulabilities of the index finger and thumb were separately similar across all subjects in tip-pinch postures. It was found that the manipulability for the cooperation of the index finger and thumb of all the subjects in tip-pinch depended on the posture of the index finger, but not on the posture of the thumb. In two-dimensional tip-pinch, it was possible that the index finger worked actively while the thumb worked passively to support the manipulation of the index finger.