Many drugs for cerebral infarction that were shown to be effective in animal experiments have shown negative results in human clinical trials. For this reason, a completely new approach is needed to develop brain protection therapies against cerebral infarction. Brain protection therapies can be categorized into 3 types: 1) lengthening the therapeutic time window for thrombolytic therapy, 2) reducing the side effects of thrombolytic therapy, and 3) brain protection drug therapy for patients with contraindications for thrombolytic therapy (including combination therapy). Here, we show our recent results of brain protection therapy. First, combination therapy with 2 effective drugs was tried, and time-lag administration was performed. Combination therapy was effective and lengthened the therapeutic time window. Next, a completely new approach to improve cerebral ischemic damage, namely, H₂ gas inhalation therapy, was tried. This therapy was also effective, even in the ischemic core.

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Chronic kidney disease (CKD) is defined as either kidney damage or an estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73 m² for more than 3 months. Kidney damage is defined as pathological abnormalities or markers of damage, including abnormalities in blood or urine tests or imaging studies. CKD is classified as stage 1 to 5 on the basis of eGFR. Cardiovascular disease (CVD) carries a reciprocal risk of loss of kidney function in patients with chronic kidney disease (CKD) and with the development of kidney disease. CVD is a major cause of morbidity and mortality in patients with CKD. Blood pressure control in patients with CKD aims to prevent CVD and provide renoprotection. The renin-angiotensin system (RAS) is involved in every stage of the progression of CKD and is, therefore, a critical link in the pathologic relationship between hypertension and renal disease. The first-line agents for controlling blood pressure are inhibitors of the RAS: angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers. These agents have been shown to have renoprotective effects in addition to their ability to control bood pressure. In CKD, the target blood pressure is less than 130/80 mm Hg, or 125/75 mm Hg, if amount of urinary protein is more than 1 g/day. To achieve the target blood pressure, other classes of antihypertensive agents, such as diuretics and calcium channel blockers, should be administered in addition to angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers.

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In this third part of a series surveying medical statistics, the concepts of correlation and regression are reviewed. In particular, methods of linear regression and logistic regression are discussed. Arguments related to survival analysis will be made in a subsequent paper.

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Inducible nitric oxide synthase (iNOS/NOS II) mediates cytotoxicity under pathological stimulation. The purpose of this study was to examine whether the blockade of NOS activity leads to a decrease in cochlear damage after intense acoustic stimulation. Guinea pigs were divided into 4 groups: (1) a noise group, (2) a NOS inhibitor (N^G-nitro-L-arginine methyl ester [L-NAME]) + noise group (L-NAME/noise group), (3) an L-NAME group, and (4) a control group. Stimuli involved a pure tone at a frequency of 2 kHz for 5 hours. The sound pressure level was 120 dBSPL. In the L-NAME/noise group, 50 mg/kg body weight of L-NAME was injected 1 hour before acoustic stimulation. In the control group and the L-NAME group, acoustic stimulation was not performed. In the L-NAME group, the same dose of L-NAME was injected intraperitoneally. In the control group, only physiological saline was injected. Auditory brainstem responses (ABRs) were recorded before and immediately, 1 day, and 7 days after acoustic stimulation. The ABR threshold was significantly higher immediately after acoustic stimulation in both the noise group and the L-NAME/noise group. One day after acoustic stimulation, the threshold shift was decreased in the noise group. The threshold shift was still present 7 days after acoustic stimulation but was significantly lower in the L-NAME/noise group than in the noise group. In the L-NAME group and the control group, threshold shifts were not apparent. The lateral wall, the organ of Corti, and the spiral ganglion cells of the cochlea in both the L-NAME group and the control group did not display immunoreactivity for iNOS at any time. Immunoreactivity for iNOS was found in the lateral wall, the supporting cells (Hensen's cells, Deiters' cells, and pillar cells), and the spiral ganglion cells in both the noise group and the L-NAME/noise group. These immunoreactivities for iNOS were detected immediately, 1 day, and 7 days after acoustic stimulation. Immunoreactivity decreased over time in the stria vascularis, the organ of Corti, and the spiral ganglion cells in the noise group. The same phenomenon was observed in the L-NAME/noise group. In conclusion, iNOS was detected in cochlea damaged by acoustic stimulation. A NOS inhibitor (L-NAME) reduced the elevation of hearing thresholds. Our results suggest that the expression of iNOS participates in the pathogenesis of cochlear damage caused by acoustic trauma.

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Rheumatoid arthritis (RA) is a chronic multisystem disease characterized by persistent joint inflammation associated with severe pain. Because RA is an immune-mediated joint disease and because type II collagen is considered an autoantigen, rodent models of arthritis using collagen type II-specific monoclonal antibodies are valuable for studying the pathogenesis of autoimmune arthritis and for evaluating therapeutic strategies. The tachykinin family peptides, substance P (SP) and hemokinin-1 (HK-1), are expressed in the nervous systems and in many peripheral organs and immunocompetent cells and activate tachykinin NK₁ receptors with similar affinities. NK₁ receptors are involved in the inflammation and hyperalgesia associated with a variety of inflammatory diseases. In the present study, we examined the involvement of SP and HK-1 in the joint inflammation and hyperalgesia in a collagen antibody-induced arthritis (CAIA) model in mice. The messenger RNA expression levels of the TAC1 gene encoding SP and of the TAC4 gene encoding HK-1 were decreased in the dorsal root ganglia and spinal cord at the peak of the inflammatory symptoms in CAIA. Systemic injection of an NK₁ receptor antagonist, WIN 51708, significantly inhibited the joint swelling, but not the mechanical allodynia, on day 7 in CAIA mice. The messenger RNA expression levels of TAC1 and TAC4 in the dorsal root ganglia and dorsal spinal cord were unaffected by treatment with WIN 51708. These findings suggest that tachykinins and NK₁ receptors play a key role in joint inflammation, rather than in nociceptive sensitization, in CAIA.

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Purpose: We investigated surgical results of staple line coverage with a polyglycolic acid sheet plus pleural abrasion by thoracoscopic surgery for treating primary spontaneous pneumothorax in young patients.
Methods: Forty-seven patients younger than 40 years underwent 48 thoracoscopic surgical procedures for spontaneous pneumothorax at the Division of Thoracic Surgery, Department of Surgery, Nippon Medical School, from May 2007 through August 2010. All patients underwent thoracoscopic bullectomy with stapling devices and pleural abrasion performed with a gauze sponge held by forceps until the pleura became petechial. Finally, the staple line was covered with a polyglycolic acid sheet (10 × 10 cm). No fibrin glue was used. We investigated both short-time results after surgery and the postoperative recurrence of pneumothorax.
Results: There was no operative mortality or morbidity, such as air leakage from staple lines or hemorrhage due to pleural abrasion. Pneumothorax recurred after surgery in 3 cases. In 2 cases, neither re-operation nor tube thoracostomy was necessary because intrapleural adhesions allowed only partial collapse of the lung. One patient underwent re-operation for an overlooked bulla facing the diaphragm in left lower lobe of the lung 2 days after the first operation. The rate of freedom from pneumothorax 4 years after surgery was 94%.
Conclusions: Staple line coverage with a polyglycolic acid sheet plus pleural abrasion by thoracoscopic surgery is a useful method for preventing morbidity and the postoperative recurrence of pneumothorax.

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This report describes creation of a bone-anchored sling with the InVance^TM system (American Medical Systems, Minnetonka, MN, USA) for the treatment of 2 patients with incontinence after radical prostatectomy. The InVance^TM system uses a silicon-coated polyester sling positioned under the bulbar urethra via a perineal incision. The sling is attached to both ischiopubic rami by 3 titanium screws. Operative times were 157 minutes (patient 1) and 240 minutes (patient 2). Blood loss was 70 mL (patient 1) and 10 mL (patient 2). The patients used 7 and 5 absorbent pads/day, respectively, before surgery and 1 and 0 pads/day after surgery (this datum does not appear in the main text, although the absence of incontinence is mentioned). The only major adverse event encountered was mesh infection necessitating mesh removal in patient 2. This operation appears comparatively simple and useful.

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We describe the surgical treatment of a patient with diaphragmatic invasion by a ruptured hepatocellular carcinoma (HCC) associated with biliary and portal venous tumor thrombi. A 67-year-old man was admitted because of jaundice (total serum bilirubin, 6.6 mg/dL). The serum concentration of alpha-fetoprotein was 236.1 ng/mL. The anti-hepatitis C virus antibodies were present in the serum. Computed tomography showed a large hypervascular mass in the right subphrenic region, surrounded by local effusion. Endoscopic retrograde cholangiography revealed dilatation of the left intrahepatic bile duct caused by biliary tumor thrombi extending from the right hepatic duct to the common bile duct. Endoscopic nasobiliary drainage was performed, and the total serum bilirubin level returned to the normal range. Angiography revealed a hypervascular tumor without extravasation of contrast medium in the right lobe and obstruction of the right anterior branch of the portal vein. Right hepatectomy was attempted 15 days after drainage. Severe invasion of the diaphragm by the ruptured HCC was detected. Bleeding of the ruptured HCC stopped spontaneously. Partial resection of the diaphragm was performed, followed by primary suture, without an artificial patch. Tumor thrombectomy was performed from the common bile duct. Macroscopic examination revealed that the ruptured HCC had invaded the diaphragm. Biliary and portal venous tumor thrombi were present. Histopathological examination showed a moderately differentiated HCC with biliary and portal venous tumor thrombi. The postoperative course was uneventful. The patient was discharged on postoperative day 14. Five months after the operation, local and intrahepatic recurrences of HCC were detected. Six months after operation, the patient died of liver failure. In conclusion, the outcome of a patient with diaphragmatic invasion by a ruptured HCC with biliary tumor thrombi was poor, even after curative hepatic resection.

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A 35-year-old man presented with simultaneous occurrence of subarachnoid hemorrhage (SAH) and cerebral infarction (CI) caused by anterior cerebral artery (ACA) dissection. He complained of sudden onset of left frontal headache and his symptoms progressed to consciousness disturbance and right hemiparesis. Computed tomography and magnetic resonance imaging demonstrated SAH localized in the left interhemispheric fissure and CI in the territory of the left ACA. Right carotid angiography demonstrated a long double lumen sign at the left A2 to A4 segment of the left ACA, leading to a diagnosis of the combined type of CI and SAH caused by ACA dissection. Although many surgeons have previously tried to perform endovascular treatment, we selected only medication in this case, and his neurological findings gradually improved. Only 9 cases including the present case presented with simultaneous occurrence of SAH and CI caused by ACA dissection. Many of these patients showed stenosis with dilatation of ACA on carotid angiography. The prognoses of these patients were good. However, many SAH patients with dissecting aneurysm had poor prognoses. To improve the strategy for managing ACA dissection, we need to accumulate a greater number of such cases in the future. We also recommend that angiography should be performed in the patients with ACA dissection.

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A 61-year-old man without a Marfan-like phenotype was admitted to the hospital because of acute Stanford type A aortic dissection. The patient underwent surgical repair with total arch replacement. Histological examination of the excised aorta showed a connective tissue abnormality, which could have contributed to the development of aortic dissection. The cause of the connective tissue abnormality could not be determined through physical examination. Recently, however, many novel gene mutations have been found to be related to aortic diseases that do not always produce physical signs and symptoms. In this case, unknown causes of connective tissue abnormalities might be existed.

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The collagen gel droplet-embedded culture drug sensitivity test (CD-DST) is one of the best chemosensitivity tests owing to its high success rate. However, CD-DST is often a culture method, and contamination is a serious problem, especially in the case of colorectal cancer, which is contaminated by enteric bacteria. It has been reported that the success rate of CD-DST is 64.0% in the case of colorectal cancer. Therefore, the sampling and washing of specimens before culture are extremely important. By washing specimens carefully with normal saline containing antibiotics, we achieved a success rate of 85.3% in the case of colorectal cancer. To improve the success rate, we started specimen irrigation with a large amount of normal saline in January 2007. As a result, a success rate exceeding 90% was acquired. For the success of CD-DST for colorectal cancer, it is important to irrigate specimens many times with a large amount of normal saline.

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