[Experience of Treatment for Pneumothorax with Coronavirus Disease 2019( COVID-19) Pneumonia].

A 73 years old male patient with the past history of kidney transplantation was admitted to our hospital for treatment of coronavirus disease 2019 (COVID-19) pneumonia. On the 25th day after the onset of symptoms when his condition was improving, he suddenly developed pneumothorax. Chest tube drainage was performed and connected the tube to the drainage device using a high efficiency particulate air (HEPA) filter. Because of the improvement of infection, the HEPA filter was removed from the drainage device on day 28. Chest tube drainage was continued by day 35, and he was discharged and introduced home oxygen therapy on day 51.

[The Early Removal of the Implant after Nuss Procedure Due to the Infection in Case of Pectus Excavatum with Atopic Dermatitis].

Nuss procedure for pediatric patients with pectus excavatum has been practiced worldwide, including in Japan, due to the simple procedure and has a high therapeutic effect. Because it is usually performed under thoracoscopy to secure the safety, it is performed not only by pediatric or plastic surgeons but also by general thoracic surgeons. On the other hand, a risk of infection must always be considered in this method in which a foreign metal bar is used. In particular, when the skin barrier mechanism is declining due to skin diseases such as atopic dermatitis, the risk of infection of the implant may increase. The present case was an 8-year-old male with a history of atopic dermatitis. He underwent thoracoscopic Nuss procedure. Although there was no problem during his hospitalization, the bar was exposed from the skin on the 58th postoperative day with the infection triggered, and the unexpected early bar removal was performed on the 66th postoperative day. We report this case with some literature review.

Evaluation of the antiviral potential of the soluble forms of glycoprotein D receptors on ocular herpes caused by HSV-1 and HSV-2 infections in a transgenic mouse model.

Ocular herpes, caused by herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) infections, remains an important corneal disease, which may result in loss of vision. Because the frequency of acyclovir resistance in HSV has increased, novel antiviral agents are needed for therapeutic approaches to ocular herpes. Several studies have demonstrated that fusion proteins containing entire ectodomain of HSV glycoprotein D receptors, including herpesvirus entry mediator A (HVEM), nectin-1 and nectin-2, and the Fc portion of human IgG (HVEMIg, nectin-1Ig, and nectin-2Ig, respectively), can exert antiviral effects in vitro and in vivo. Here, to evaluate the antiviral potential of HVEMIg, nectin-1Ig, and nectin-2Ig against ocular infections with HSV, transgenic mice expressing these fusion proteins were ocularly inoculated with HSV-1 and HSV-2. Transgenic mouse lines expressing HVEMIg and nectin-1Ig showed marked resistance to ocular herpes; on the other hand, mouse lines expressing nectin-2Ig did not. Furthermore, to investigate the therapeutic effects of nectin-1Ig, which can neutralize HSVs in vitro against ocular disease, transgenic mouse serum containing nectin-1Ig was dropped into the eyes of wild-type mice after HSV infection. Reduction of severe symptoms could be observed in mice treated with nectin-1Ig serum. These results warrant further study of soluble HVEM and nectin-1 products as preventive and therapeutic agents against ocular herpes caused by HSV-1 and HSV-2 infections, especially nectin-1Ig as a new eye drop.

Comparison of the antiviral potential among soluble forms of herpes simplex virus type-2 glycoprotein D receptors, herpes virus entry mediator A, nectin-1 and nectin-2, in transgenic mice.

Herpesvirus entry mediator A (HVEM), nectin-1 and nectin-2 are cellular receptors of glycoprotein D (gD) of herpes simplex virus type-2 (HSV-2). It has been shown that soluble forms of HSV gD receptors have the antiviral potential in cultured cells and transgenic mice. Here, to compare antiviral potential of soluble forms of HVEM, nectin-1 and nectin-2 against HSV-2 infections in vivo, transgenic mice expressing fusion proteins consisting of the entire ectodomain of HVEM, nectin-1 or nectin-2 and the Fc portion of human IgG (HVEMIg, nectin-1Ig and nectin-2Ig, respectively) were intraperitoneally infected with HSV-2. In the infection with 3 MLD50 (50 % mouse lethal dose), effective resistance was not observed in transgenic mice expressing nectin-2Ig. In a transgenic mouse line with high expression of nectin-1Ig, significant protection from the infection with 30 and 300 MLD50 was observed (survival rate of 100 and 71 %, respectively). On the other hand, transgenic mice expressing HVEMIg showed a complete resistance to the lethal infection even with 300 MLD50 (survival rate of 100 %). These results demonstrated that HVEMIg could exert effective antiviral activities against HSV-2 infections in vivo as compared with other soluble forms of HSV gD receptors.

Factors related to the urination methods of elderly people with incontinence who require at-home nursing care.

OBJECTIVE: This study aimed to elucidate the urination status among elderly people with incontinence who require at-home nursing care as well as the status of their family caregivers, and to identify the factors related to their urination methods. METHODS: In the present study, questionnaires were distributed to 101 elderly subjects (n=101) and their caregivers. RESULTS: The most prevalent urination method was the collaboration of toilet and adult diapers (69, 68.8%).There was a significantly larger number of patients who used a toilet <4 times and who had a "moderate" amount of incontinence and patients who used toilet 4-8 times and had a "slight" amount of incontinence (p<0.05). We performed a multivariate logistic regression analysis using the stepwise method. We used 8 items from the responses of the elderly subjects and their caregivers that were identified as being independently associated with the urination method using the chi-squared test (or Fisher's exact probability test), with the urination method as the dependent variable. Among elderly people, the ability to use a toilet properly (p=0.004) and independent mobility (p=0.028) strongly influenced their use of a toilet for urination. Among caregivers, the influencing factor was not thinking that they have to use the toilet even though they are unable to urinate (p=0.027). CONCLUSION: The use of a toilet for urination by elderly people was influenced by their physical functions and by the caregivers' attitudes toward excretion-related nursing care. When providing urination assistance, it is important for caregivers to maintain the physical functions of the elderly by providing support when necessary. It is also important to assess the bladder function by, methods such, as measuring the amount of residual urine and cooperate with a physician.

Single amino acid mutation of nectin-1 provides remarkable resistance against lethal pseudorabies virus infection in mice.

An approach to genetically engineered resistance to pseudorabies virus (PRV) infection was examined by using a mouse model with defined point mutation in primary receptor for alphaherpesviruses, nectin-1, by the CRISPR/Cas9 system. It has become clear that phenylalanine at position 129 of nectin-1 is important for binding to viral glycoprotein D (gD), and mutation of phenylalanine 129 to alanine (F129A) prevents nectin-1 binding to gD and virus entry in vitro. Here, to assess the antiviral potential of the single amino acid mutation of nectin-1, F129A, in vivo, we generated genome-edited mutant mouse lines; F129A and 135 knockout (KO). The latter, 135 KO used as a nectin-1 knockout line for comparison, expresses a carboxy-terminal deleted polypeptide consisting of 135 amino acids without phenylalanine 129. In the challenge with 10 LD50 PRV via intranasal route, perfect protection of disease onset was induced by expression of the mutation of nectin-1, F129A (survival rate: 100% in F129A and 135 KO versus 0% in wild type mice). Neither viral DNA/antigens nor pathological changes were detected in F129A, suggesting that viral entry was prevented at the primary site in natural infection. In the challenge with 50 LD50 PRV, lower but still strong protective effect against disease onset was observed (survival rate: 57% in F129A and 75% in 135 KO versus 0% in wild type mice). The present results indicate that single amino acid mutation of nectin-1 F129A provides significant resistance against lethal pseudorabies.

[Assessment of hand-foot syndrome in cancer patients treated with capecitabine-containing chemotherapy].

Capecitabine is one of the most effective oral chemotherapeutic drugs for advanced or recurrent colorectal cancer and gastric cancer. Capecitabine-containing chemotherapy is recommended as a first-line option for gastrointestinal tract cancer. The incidence of hand-foot syndrome (HFS), an adverse event of chemotherapy with capecitabine, is high. Moreover, once the symptoms of HFS are identified, they can significantly impair the quality of life (QOL) of patients. HFS should be managed by dose interruption and, if necessary, by dose reduction. Pharmacists and oncology nurses play an increasingly important role in the early identification and prevention of HFS through patient education and close clinical assessment. The aim of this study was to evaluate the efficacy of support tools for the early identification, prevention, and management of HFS and to assess the effectiveness of "patient self-check sheets". The patient was detected as having HFS of mild severity and had used a moisturizer at the time of initiation of therapy. Maintaining moisture retention is important in the management of HFS. The ambulatory team plays a key role by using self-check sheets to educate patients on how to recognize HFS, when to interrupt treatment, and how to adjust the dose so as to maintain effective therapy with capecitabine. For the continuation and completion of treatment and for maintaining an improved QOL in the home environment, supportive measures for adverse effects such as HFS and an ambulatory team are indispensable.

Two cases of male nipple leiomyoma: idiopathic leiomyoma and gynecomastia-associated leiomyoma.

We describe 2 cases of male nipple leiomyoma. A 70-year-old man had a painful subcutaneous tumor on his left nipple of 6 months duration. Histopathology disclosed dermal spindle cells with oval-shaped nuclei forming interlacing bundles with irregular pattern. Glandular elements were absent. The spindle cells were positive to α-smooth muscle actin, desmin, and vimentin. Estrogen receptor (ER) and progesterone receptor (PrR) were negative. We diagnosed this case as male leiomyoma of the nipple. Another patient was a 61-year-old man with gynecomastia induced by spironolactone of 6 months duration. He also had a painful nodule on his left nipple and histopathology disclosed spindle-shaped tumor cells as in the previous patient. The tumor was accompanied by glandular elements in the deep dermis and subcutaneous tissue, which showed apocrine secretion and were positive for α-smooth muscle actin, ER, and PrR. These glandular elements were interpreted as mammary gland. But ER and PrR stain did not show positive results for leiomyoma in the upper dermis. To the best of our knowledge, this is the first report of male idiopathic and gynecomastia-induced leiomyoma with ER and PrR staining.

[Assessment of hand-foot syndrome in cancer outpatients undergoing chemotherapy].

Capecitabine, an oral prodrug of 5 -fluorouracil, is a promising treatment for colorectal, breast, and gastric cancers, but often causes hand-foot syndrome(HFS), which is the most common dose-limiting toxicity. The aim of this study was to evaluate of the efficacy of the pharmacist in providing support at ambulatory therapy centers, especially for HFS. The HFS is a higher-incidence adverse event that may develop during chemotherapy with capecitabine. Once developed, the symptoms significantly impair quality of life(QOL), leading to a reduction in the dosage or discontinuation of the treatment. Patient symptoms may therefore increase in severity. This study was performed to analyze the treatment adherence and adverse events resulting from capecitabine therapy provided by pharmacists to cancer outpatients. All patients were prescribed vitamin B6(pyridoxine), which can help to reduce or prevent HFS. A lesser or milder extent of HFS was detected in patients who had used a moisturizer at the same time as the introduction of capecitabine therapy. Adherence to this approach will benefit the patients' selfcare in maintaining moisture retention, which is an important countermeasure for HFS. Additionally, early introduction of effective countermeasures for skin care, dose reduction, and rest periods is important for HFS management; in addition, team care support is dispensable. Our support system may be useful for management strategies for HFS. We suggest that improved quality of lif e is needed in cancer outpatients being treated with chemotherapy.

The risk of footswitch misstep during robot-assisted thoracoscopic surgery: a case report.

The Da Vinci Surgical System is an ergonomically devised and excellent surgical support device. However, surgeon skill is of paramount importance since human error cannot be completely eliminated. We report a case of bleeding from the pulmonary artery due to a footswitch misstep. A 72-year-old male with suspected right upper lobe lung cancer underwent robot-assisted thoracoscopic surgery (RATS). While avoiding the pulmonary artery with the right arm spatula and trying to cauterize V2t with the left arm bipolar-forceps, the footswitch was accidently activated and the spatula was energized, resulting in pulmonary artery trauma and blood loss. After this case, we changed the surgical procedure from a monopolar-bipolar combination use to a bipolar-only use and noted no significant difference in the console duration, and less intraoperative blood loss. Human errors can occur anytime. Especially for surgeons new to RATS, simplified foot management should be considered until RATS mastery is achieved.

Antiviral effects against influenza A virus infection by a short hairpin RNA targeting the non-coding terminal region of the viral nucleoprotein gene.

RNA interference (RNAi) can inhibit Influenza A virus (IAV) infection in a gene-specific manner. In this study, we constructed a transgene expressing a short hairpin RNA (shRNA) that targets the noncoding region of the IAV RNA gene encoding nucleoprotein (NP). To investigate the antiviral effects of the shRNA, we generated two transgenic mouse lines with this transgene. Unfortunately, there was no apparent difference in IAV resistance between transgenic and non-transgenic littermates. To further investigate the antiviral effects of the shRNA, we prepared mouse embryonic fibroblasts (MEFs) from transgenic and non-transgenic mice. In experimental infections using these MEFs, virus production of mouse-adapted IAV strain A/Puerto Rico/8/1934 (PR8) in the transgenic MEFs was suppressed by means of the down-regulation of the viral RNA gene transcription in the early stages of infection in comparison with non-transgenic MEFs. These results indicated that expression of the shRNA was able to confer antiviral properties against IAVs to MEFs, although the effects were limited. Our findings suggest that the shRNA targeting the noncoding region of the viral RNA (vRNA) of NP might be a supporting tool in developing influenza-resistant poultry.

Hemorrhagic Gastric Metastasis from Hepatocellular Carcinoma Successfully Treated Using Coil Embolization of the Left Gastric Artery.

A 62-year-old man initially underwent transcatheter arterial chemoembolization for the treatment of hepatocellular carcinoma (HCC). One year after the initial treatment, he developed anemia. Upper gastrointestinal endoscopy revealed irregularly elevated tumors in the lower anterior gastric body, which were diagnosed to be metastasis from HCC. Left gastric artery coil embolization was performed to prevent sustained bleeding, and his anemia partially improved. In addition to direct invasion, hematogenous metastasis to the stomach from HCC is possible and therefore should be considered during treatment. Transcatheter arterial embolization for gastric metastasis is an effective treatment method which achieves a good degree of hemostasis in patients without any surgical indications.

Four new diterpenoid alkaloids from Aconitum japonicum subsp. subcuneatum.

Diterpenoid alkaloids with remarkable chemical properties and biological activities are frequently found in plants of the genera Aconitum, Delphinium, and Garrya. Accordingly, several diterpenoid alkaloid constituents of Aconitum and Delphinium plants as well as their derivatives exhibited cytotoxic activity against lung, prostate, nasopharyngeal, and vincristine-resistant nasopharyngeal cancer cell lines. Four new C19-diterpenoid alkaloids, 14-anisoyllasianine (1), 14-anisoyl-N-deethylaconine (2), N-deethylaljesaconitine A (3), and N-deethylnevadensine (4), together with 17 known C19- and C20-diterpenoid alkaloids, were isolated in a phytochemical investigation of rhizoma of Aconitum japonicum THUNB. subsp. subcuneatum (NAKAI) KADOTA. Their structures were elucidated by extensive spectroscopic methods including NMR (1D and 2D), IR, and MS (HRMS). Eight known diterpenoid alkaloids, lipoaconitine, lipomesaconitine, aconine, nevadenine, talatisamine, nevadensine, ryosenamine, and dehydrolucidusculine, were isolated the first time from A. japonicum subsp. subcuneatum. Three of the new C19-diterpenoid alkaloids (1, 3, 4) and six of the known diterpenoid alkaloids were evaluated for cytotoxic activity against five human tumor cell lines.

Angiotensin-II administration is useful for the detection of liver metastasis from pancreatic cancer during pharmacoangiographic computed tomography.

AIM: To improve the preoperative diagnosis of liver metastasis from pancreatic cancer, we estimated computed tomography during arterial angiography (CTA) with/without administration of angiotensin-II (AT- II). METHODS: Thirty-five patients with pancreatic cancer were examined in this study. After conventional CTA was performed, pharmacoangiographic CTA was performed with a 1-3 microgram/5 mL solution of angiotensin II injected through a catheter into the celiac artery during spiral computed tomography. We prospectively analyzed the relative region of interest (ROI) ratio of tumor to liver with/without AT-II. RESULTS: In all patients, the relative ratio of each computed tomography (CT) number in the ROI was larger at pharmacoangiographic CT than at conventional angiographic CT. Administration of angiotensin-II enhanced the metastatic liver tumor as compared with normal tissue. Intratumoral blood flow increased in all patients with malignant tumors due to the pressure effect of AT-II. Furthermore, the metastatic lesions in the liver of three patients were represented by only pharmacoangiographic CT, not by conventional CT and conventional CT angiography. In even peripheral and central areas of metastatic liver tumor, the lesions were enhanced after administration of AT-II. CONCLUSION: These results support that high detection rate of liver metastasis revealed by pharmacoangiographic CT suggests the improvement of diagnosis on preoperative staging. Moreover, chemotherapy under AT-II induced hypertension may have a better effect on the treatment of metastatic liver tumors.

Clinical efficacy of intra-arterial pharmacokinetic chemotherapy with 5-fluorouracil, CDDP, gemcitabine, and angiotensin-II in patients with advanced pancreatic cancer.

BACKGROUND/AIMS: To deliver anticancer drugs more selectively into cancer tissues and to improve survival time, we have developed a new method of intra-arterial chemotherapy for unresectable pancreatic cancer. METHODOLOGY: From April 2002 to June 2006, twenty patients with pancreatic cancer with liver metastases were given intra-arterial infusions consisting of gemcitabine, 5-FU, and cisplatin mixed with angiotensin-II with the intent of increasing the blood flow into the tumor tissue but decreasing that to the non-tumor tissues. Simultaneously, tegafur/uracil was administered. A tumor marker and computed tomography (CT) findings were used to evaluate the efficacy of this chemotherapy. RESULTS: The median survival was 365 days, and 6-months and 1-year survival rates were 80.0% and 44.7%, respectively. In 12 of 20 cases, the tumor marker level was decreased after this chemotherapy. In 10 of 20 cases, computed tomography showed a decrease in the tumor size. In 6 patients, back pain was the chief complaint and was reduced to a self-controlled level in 20 patients. No major complications were encountered. CONCLUSIONS: Compared with the previously reported data in traditional chemotherapies, our method of intra-arterial chemotherapy appears to be quite useful not only for prolonging patient survival but also for improving the quality of life. Intra-arterial regional chemotherapy including changes in distribution of blood flow induced by angiotensin-II appears to be an effective palliative treatment for advanced pancreatic cancer.

[A resected case of fibrolamellar hepatocellular carcinoma with chronic hepatitis (type B)].

We report a case of a 34-year-old woman who tested positive for HBs Ag with fibrolamellar hepatocellular carcinoma of the liver. The sister of this patient, who was also positive for HBs Ag, died of hepatocellular carcinoma (HCC). The patient showed elevation of alpha-fetoprotein. Abdominal CT scan showed a tumor in the posterior segment of the liver and hepatic angiography revealed marked neovascularity in the tumor. Partial resection of the liver was performed, and the histological diagnosis was fibrolamellar hepatocellular carcinoma. The patient is now tumor free and doing well 20 months after the operation.

[A case of splenic inflammatory pseudotumor].

A 59-year-old man was admitted to our hospital because of continuous C-reactive protein elevation. Abdominal computed tomography scan revealed a low density mass on the surface of the spleen. Magnetic resonance imaging showed low intensity at peripheral area and slightly high intensity in the central area of the mass lesion on T1 and T2-weighted image. Splenectomy was performed since we could not rule out the possibility of malignant neoplasm only by diagnostic imaging. The pathological diagnosis of the tumor was inflammatory pseudotumor. Splenectomy is considered to be significant from the standpoints of both diagnosis and therapy in cases in which diagnostic imaging is difficult to interpret.

Expression of zinc finger protein ZPR1 mRNA in brain is up-regulated in mice fed a high-fat diet.

A differential display was performed to analyze differential gene expression in the brain of mice in association with dietary high beef tallow. Consumption of a high beef tallow diet up-regulated the expression of zinc finger protein ZPR1 mRNA in the brain. Expression of ZPR1 mRNA in the cerebellum and hippocampus was elevated in response to the high beef tallow diet. The increased ZPR1 expression in the neuronal, Neuro-2A cells, caused a significant increase in H(2)O(2)-induced cell death. These results suggest that a high beef tallow diet up-regulates ZPR1 mRNA expression in the brain and might increase the vulnerability to oxidative stress.