Factors predicting early postoperative liver cirrhosis-related complications after lung cancer surgery in patients with liver cirrhosis

We aimed to determine the factors predicting liver cirrhosis-related complications in the early postoperative period after lung cancer surgery in patients with liver cirrhosis. We retrospectively reviewed the medical records of patients who underwent curative surgery for primary lung cancer in our institute from January 1990 to March 2007, finding 37 cases with comorbid liver cirrhosis. These patients were divided into two groups, according to whether liver failure, bleeding, and critical infection had occurred postoperatively. Various clinical parameters were analyzed statistically between the bigeminal groups. Liver cirrhosis-related complications occurred in seven of the 37 patients (18.9%). Transient liver failure occurred in two patients (5.4%) after pulmonary resection. Acute intrathoracic bleeding occurred in four cases (10.8%). Two patients died (5.4%) in both cases due to sepsis. Preoperative total bilirubin (P<0.05), and indocyanine green retention rate at 15 min (P<0.05) were significantly higher in patients with liver failure. Only serum value of total bilirubin was an independent risk factor (P<0.05) by multivariate analysis. In predicting death from infection, only preoperative nutritional status was a significant risk factor (P<0.05). To avoid postoperative cirrhosis-related complications, preoperative preparation to improve their liver function and nutrition status is essential.     

Fungal meningitic hydrocephalus with repeated shunt malfunction

A 33-year-old female presented with a rare case of fungal meningitis caused by Aspergillus detected for the first time at 15 years after onset. The meningitis repeatedly occurred over a period of 15 years. On admission, cerebrospinal fluid examination found cell count 1340/high-power field, protein 158 mg/dl, and sugar 8 mg/dl, indicating meningitis, although no bacterial or fungal species were detected. Cerebral computed tomography demonstrated hydrocephalus and cervical computed tomography demonstrated a mass lesion on the ventral side of the spinal cord from C4 to C6. Fungal meningitis was suspected and treated with amphotericin B. Her symptoms improved and she was eventually discharged. She was readmitted for recurrence of meningitis and hydrocephalus 2 months later. Amphotericin B was administered and a ventriculoperitoneal (VP) shunt was placed. Shunt malfunction recurred seven times. Aspergillus was detected for the first time from the atrium side of the ventriculoatrial shunt tube at 15 years after onset. Fluconazole was administered. She had narrowing of the cisterna magna, and underwent foramen magnum decompression. The VP shunt was finally reconstructed. Fluconazole administration was continued. Combination of foramen magnum decompression and long-term administration of fluconazole was effective in this case.     

Survey of Glycyrrhizae Radix resources in Mongolia: chemical assessment of the underground part of Glycyrrhiza uralensis and comparison with Chinese Glycyrrhizea Radix

In order to reveal the chemical characteristics of Glycyrrhiza uralensis growing in Mongolia and to clarify whether it can be the source of Glycyrrhizae Radix used in Japan, eight major bioactive constituents in the underground parts of G. uralensis collected in Mongolia were quantitatively analyzed and compared with Glycyrrhizae Radix produced in China. Most of the 15 samples from eastern, southern and western parts of Mongolia contained 26.95–58.55 mg/g of glycyrrhizin, exceeding the criterion (25 mg/g) assigned in the Japanese Pharmacopoeia. The sample collected in Tamsagiyn hooly, Dornod province, in eastern Mongolia was of the highest content 58.55 mg/g. The contents of three flavanone constituents (liquiritin apioside, liquiritin and liquiritigenin) and three chalcones (isoliquiritin apioside, isoliquiritin and isoliquiritigenin) varied significantly according to collection places; the subtotal of the three flavanones ranged from 3.00 to 26.35 mg/g, and the subtotal of the three chalcones ranged from 1.13 to 10.50 mg/g. The content of glycyrrhizin and subtotal contents of flavanones and chalcones in the underground parts of G. uralensis from Mongolia were obviously lower than wild samples, but higher than cultivated samples derived from the same species produced in China. Glycycoumarin, a species-specific constituent of G. uralensis, was detected in all Mongolian samples. Its contents in samples from eastern Mongolia, Sergelen and Tamsagiyn hooly of Dornod province were very high and were compatible with Tohoku-kanzo derived from wild Chinese G. uralensis. The present study suggested that Mongolian G. uralensis could be a source of Glycyrrhizae Radix, mostly of Japanese Pharmacopoeia grade. However, the producing area should be taken into consideration to ensure relatively high quality. In addition, planned use and promotion of cultivation must be advocated to avoid confronting Mongolian Glycyrrhiza with the same threat as its congener in China. Our study sheds some light on selecting cultivation areas and superior strains, which are important tasks to promote cultivation.     

Nitric oxide generation directly responds to ultrasound exposure

Recently, several reports have been published on ultrasonic vascular dilation produced with relatively low-frequency ultrasound. It has been speculated that nitric oxide (NO) is an important factor for this ultrasonic vascular dilation. However, a quantitative relationship between the ultrasound intensity and NO generation was not clarified in these reports. We investigated the quantity of NO generated by various ultrasonic intensities by means of real-time measurement of NO concentration in the adductor muscles of the thigh of New Zealand white rabbits exposed to a continuous-wave ultrasound (490 kHz). In the quantitative relationship between NO generation and ultrasonic intensity, the percent increase in NO concentration was 1.25% +/- 1.25%, 10.6% +/- 2.9% and 20.1% +/- 3.5%, with the maximum muscle temperature increase 0.5 +/- 0.2 degrees C, 0.7 +/- 0.2 degrees C, and 0.8 +/- 0.3 degrees C at the ultrasonic intensity (SPTA) of 0.21, 0.35 and 0.48 W/cm(2), respectively. The effect of ultrasound on NO generation was intensity-dependent with a progressive increase from 0.21 W/cm(2) to 0.48 W/cm(2) without significant thermal effect. Ultrasonic NO generation was partially reduced by NOS inhibitor of L-NMMA, clarifying that ultrasound can activate both NOS-dependent and NOS-independent NO generation. These new findings provided scientific basis for ultrasonic vasodilatation and support the potentiality of a new ultrasonic technology for the treatment and prevention of the ischemic tissue based on the new concept of NO generated angiogenesis. (E-mail: furuhata@jikei.ac.jp).     

Effects of developmental hypothyroidism induced by maternal administration of methimazole or propylthiouracil on the immune system of rats

Methimazole (MMI) and propylthiouracil (PTU) are popularly used antithyroid drugs (ATDs) for the treatment of Graves' hyperthyroidism. The aim of the present study was to determine the effects of ATDs on the developing immune system of the rats. Maternal Sprague-Dawley rats were given drinking water containing 200 ppm of MMI, 12 ppm of PTU (high-dose PTU), or 3 ppm of PTU (low-dose PTU) between gestational day (GD) 10 and postnatal week (PNW) 3. Exposure to the ATDs was ceased upon weaning at PNW3, and the male offspring were sampled at PNWs 3 or 11. The serum thyroid-related hormone levels and the hematological components in the offspring were then determined. The expressions of surface markers in the spleen, thymus and peripheral blood were determined using flowcytometry. The weights of the body, spleen and thymus and the splenic and thymic cell numbers were decreased in the MMI-treated and the high-dose PTU-treated animals at PNWs 3 and 11. The serum levels of thyroid-related hormones were depressed in the MMI and high-dose PTU groups. FACS analysis revealed that the ATDs caused proportional changes in the lymphoid cell subpopulations. The proportion of B cells among the total lymphocytes was significantly decreased at PNW3, whereas that of T cells, especially of inactive T cells, was dramatically increased. Moreover, the proportion of CD4(+)CD25(+) regulatory T cells was significantly increased in the spleen and peripheral blood at PNW3. Most of the above-described changes had recovered to normal levels at PNW11. These results suggest that ATDs might have temporal immunomodulatory effects on the developing immune system.     

Anesthetic management of a patient with aortocaval fistula

Aortocaval fistula is a rare complication of ruptured abdominal aortic aneurysm (AAA), and patients with an aortocaval fistula show multiple symptoms. We report an 87-year-old man who was diagnosed as having an AAA with aortocaval fistula and who developed refractory hypotension after induction of anesthesia. Following a phenylephrine injection for slight hypotension induced by anesthetic induction, he developed severe hypotension and bradycardia, and his skin became cyanotic. Vasopressor agents had no immediate effect on the hypotension, but blood pressure gradually increased in about 30 min with continuous infusion of dopamine and noradrenaline. Transesophageal echocardiography (TEE) showed right ventricle (RV) hypokinesis and massive tricuspid regurgitation (TR). Central venous pressure (CVP) showed a remarkably high value. After the repair of the aortocaval fistula, the hemodynamics became stable, RV motion was improved, TR was reduced, and CVP became normal. Anesthetic management of the repair of an aortocaval fistula is very difficult. The hemodynamics changed dramatically throughout anesthesia in our patient with this disorder, even though low-dose anesthetics were used. For the successful treatment of this disorder, preparation for the operation is required before the induction of anesthesia, and urgent closure of the fistula is necessary after the induction of anesthesia. TEE is a useful tool for monitoring hemodynamics in such patients.     

Emerging Genotypes of Human Respiratory Syncytial Virus Subgroup A among Patients in Japan

Human respiratory syncytial virus (HRSV) is a common etiological agent of acute lower respiratory tract disease in infants. We report the molecular epidemiology of HRSV in Niigata, Japan, over six successive seasons (from 2001 to 2007) and the emerging genotypes of HRSV subgroup A (HRSV-A) strains. A total of 488 HRSV samples were obtained from 1,103 screened cases in a pediatric clinic in Niigata. According to the phylogenetic analysis, among the PCR-positive samples, 338 HRSV-A strains clustered into the previously reported genotypes GA5 and GA7 and two novel genotypes, NA1 and NA2, which were genetically close to GA2 strains. One hundred fifty HRSV-B strains clustered into three genotypes, namely, GB3, SAB3, and BA, which has a 60-nucleotide insertion in the second hypervariable region of the G protein. The NA1 strains emerged first, in the 2004-2005 season, and subsequently, the NA2 strain emerged in the 2005-2006 season. Both strains caused large epidemics in the 2005-2006 and 2006-2007 seasons. The average age of children who were infected with NA2 strains was significantly higher than that of those infected with GA5 and the frequency of reinfection by NA2 was the highest among all genotypes, suggesting that this genotype possessed new antigenicity for evading past host immunity. This is the first paper to show a possible correlation between an emerging genotype, NA2, and large outbreaks of HRSV in Japan. Continuing studies to follow up the genetic changes and to clarify the mechanism of reinfection in HRSV are important steps to understand HRSV infections.Human respiratory syncytial virus (HRSV) is the most common cause of serious acute lower respiratory tract disease among infants and young children, and is found mainly in late fall, winter, and spring in temperate zones of the world (6). Some 50% to 70% of infants experience infection in the first year of life, and virtually all are infected by 2 years of age (3). In a population-based birth cohort study, 1.1% of the cohort were admitted to the hospital within 12 months of birth with HRSV-induced bronchiolitis (14). The consequences of HRSV infection in children with underlying conditions, such as prematurity, cardiac and pulmonary disease, or immunosuppression, may include prolonged substantial illness and even death (18, 38). Reinfections are very common throughout life (7, 10, 11, 13).HRSV belongs to the family Paramyxoviridae and has a nonsegmented, negative-sense RNA genome of approximately 15,200 nucleotides (3). HRSV has been classified into antigenic subgroups A and B (HRSV-A and HRSV-B, respectively), initially on the basis of the reactivity of the virus with monoclonal antibodies directed against the attachment glycoprotein (G protein) (1, 5, 15, 21) and now by genetic analyses (9, 19, 31-33).The G protein is the most variable HRSV protein, with two hypervariable regions. Its C-terminal region (the second hypervariable region) accounts for strain-specific epitopes (2-4, 9, 16, 27, 29, 31). The molecular epidemiology and evolutionary patterns of the G protein have provided important information about the epidemiological features of HRSV. Some studies showed that several different genotypes cocirculated and some predominated in a community every year (23, 27). However, the relationship between strain diversity and the clinical and epidemiological features of HRSV has yet to be elucidated in detail.The subgroups have been subdivided further, into genotypes, by genetic analyses. HRSV-A is divided into seven genotypes (GA1 to -7) and HRSV-B into four genotypes (GB1 to -4) (3, 8). An additional HRSV-A genotype, SAA1, has been proposed, as well as the new HRSV-B genotypes SAB1 to -3 (37). Another HRSV-B genotype includes the Buenos Aires (BA) type strain, which has a 60-nucleotide insertion in the second hypervariable region of the G protein and has been reported in Buenos Aires in 1999, as well as in other areas of the world (31, 35, 40). BA strains are further subdivided into six clusters (BA-I to BA-VI) (36).National surveillance of HRSV infection based on weekly reports from sentinel pediatric clinics throughout Japan began in November 2003 under the Infectious Disease Control Law. The surveillance indicated that the number of HRSV-infected patients increased dramatically for unknown reasons in the 2005-2006 and 2006-2007 seasons. This study reports large HRSV-A epidemics in the 2005-2006 and 2006-2007 seasons in Niigata, Japan, and provides a possible link to high-level circulation in the same seasons nationwide. It also discusses the relationship between antigenic variation and clinical features of HRSV in regard to molecular epidemiology and the evolutionary patterns of the G protein.     

In Vivo and In Vitro Alterations in Influenza A/H3N2 Virus M2 and Hemagglutinin Genes: Effect of Passage in MDCK-SIAT1 Cells and Conventional MDCK Cells

No mutations were detected in the hemagglutinin gene of influenza A/H3N2 virus isolates from patients undergoing short-term amantadine treatment. However, genetic changes occurred after serial passage in either MDCK or MDCK-SIAT1 cells. Our results showed that only a few mutations were observed in MDCK-SIAT1-passaged isolates in the presence of amantadine.     

The driving system for hippocampal theta in the brainstem: An examination by single neuron recording in urethane-anesthetized rats

The brainstem has been shown to be involved in generating hippocampal theta; however, which brainstem region plays the most important role in generating the rhythm has remained unclear. To reveal which brainstem region triggers the theta, the hippocampal local field potential was recorded simultaneously with single unit activity in the brainstem of urethane-anesthetized rat. The firing latencies before theta onset and offset were compared among recording sites (deep mesencephalic nucleus, DpMe; pedunculopontine tegmental nucleus, PPT; nucleus pontis oralis, PnO). We examined the activities of 59 cells; PPT showed the highest proportion of neurons changing their firing rates at theta onset (14/16, 87.5%). The proportion in the PnO was 14/22 (63.6%), but the neurons in the PnO showed the earliest changes in latencies (0.57 s before theta onset). The change in the PPT was 0.96 s after theta onset. Regarding the theta offset, the PPT showed the highest proportion of neurons changing their firing rates at theta offset (9/16, 56.3%; the proportion in the PnO was 5/22, 22.7%), but the difference in latent time was not significant among recorded regions. The neurons in the DpMe did not show any remarkable firing tendency at theta onset and offset. From these results, we propose a driving system of hippocampal theta, in which neurons in the PnO first trigger the theta onset and then those in the PPT maintain the theta by activating broadly the brainstem areas for the wave.