Response control of RPLGD for gamma-ray dose measurement using lead filters for BNCT.

Boron Neutron Capture Therapy (BNCT) is a cell-selective radiotherapy using a neutron capture reaction of 10B. In recent years, Accelerator Based Neutron Sources (ABNS) are under development instead of nuclear reactors for the next-generation neutron irradiation system for BNCT. However, ABNS as well as nuclear reactor usually generates unavoidable secondary gamma-rays by neutron-nuclear reactions such as capture reaction. In this research, we aimed to develop a separate measurement method of only gamma-rays in a mixed field of neutrons and gamma-rays using a fluorescent glass dosimeter (RPLGD), because most dosimeters have sensitivity to both radiation types. For this purpose, we proposed a lead filter method using two RPLGDs and lead filters. However, this method has a problem that the sensitivity to low energy gamma-rays (∼100 keV) is very small. In order to improve the sensitivity to low energy gamma-rays, we devised a method using a specially shaped lead filter. From theoretical calculations, we have shown that it was possible to estimate the air dose rate of the field where the gamma-ray energy spectrum shape was known for energies up to 10 MeV. In addition, we produced the specially shaped lead filter and experimentally confirmed the validity of the lead filter method using several gamma-ray standard sources and by measurements in a nuclear fuel storage room.

Dietary carbohydrate influences the colocalization pattern of Glucagon-like Peptide-1 with neurotensin in the chicken ileum.

Glucagon-like peptide (GLP)-1 colocalizes with neurotensin (NT) in the same enteroendocrine cells (EECs) of the chicken ileum. The present study was designed to clarify the influence of dietary carbohydrate (CHO) on the colocalization pattern of GLP-1 with NT in the chicken distal ileum. Male White Leghorn chickens at 6 weeks of age (n = 15) were divided into three groups, a control and two experimental (low-CHO and CHO-free), with five chickens in each, and fed control or experimental diets for 7 d. Distal ileum was collected from each bird as a tissue sample and subjected to double immunofluorescence staining to detect GLP-1 and NT. Three types of EEC, GLP-1+/NT+, GLP-1+/NT- and GLP-1-/NT+, were demonstrated in the chicken ileum. GLP-1+/NT+ cells in the control group had a spindle-like shape with a long cytoplasmic process, but those in the experimental groups were round and lacked a cytoplasmic process. The ratio of GLP-1+/NT+ cells was significantly decreased in the two experimental groups compared with that in the control group. The ratio of GLP-1+/NT+ cells was significantly lower than those of GLP-1+/NT- and GLP-1-/NT+ cells in the two experimental groups. Most cells that were immunoreactive for GLP-1 and NT antisera lacked signals of proglucagon (PG) and NT precursor (NTP) mRNA in the experimental groups. The number of EECs expressing PG and NTP mRNA signals showed tendencies for decreases with a reduction of dietary CHO level. These findings suggest that dietary CHO could be a significant regulator of the pattern of colocalization pattern of GLP-1 with NT in the chicken ileum.

Preoperative MRI for predicting pathological changes associated with surgical difficulty during laparoscopic cholecystectomy for acute cholecystitis.

BACKGROUND: Severe inflammation with necrosis and fibrosis of the gallbladder in acute cholecystitis increases operative difficulty during laparoscopic cholecystectomy. This study aimed to assess the use of preoperative MRI in predicting pathological changes of the gallbladder associated with surgical difficulty. METHODS: Patients who underwent both preoperative MRI and early cholecystectomy for acute cholecystitis between 2012 and 2018 were identified retrospectively. On the basis of the layered pattern of the gallbladder wall on MRI, patients were classified into three groups: high signal intensity (HSI), intermediate signal intensity (ISI), and low signal intensity (LSI). The endpoint was the presence of pathological changes of the gallbladder associated with surgical difficulty, such as necrosis, abscess formation and fibrosis. RESULTS: Of 229 eligible patients, pathological changes associated with surgical difficulty were found in 17 (27 per cent) of 62 patients in the HSI group, 84 (85 per cent) of 99 patients in the ISI group, and 66 (97 per cent) of 68 patients in the LSI group (P < 0·001). For detecting these changes, intermediate to low signal intensity of the gallbladder wall had a sensitivity of 90 (95 per cent c.i. 84 to 94) per cent, specificity of 73 (60 to 83) per cent and accuracy of 85 (80 to 90) per cent. CONCLUSION: Preoperative MRI predicted pathological changes associated with surgical difficulty during laparoscopic cholecystectomy for acute cholecystitis.

ANTECEDENTES: La inflamación grave con necrosis y fibrosis de la vesícula biliar en la colecistitis aguda aumenta la dificultad quirúrgica durante la colecistectomía laparoscópica. Este estudio tuvo como objetivo evaluar el uso de la resonancia magnética preoperatoria (magnetic resonance imaging, MRI) para predecir los cambios patológicos de la vesícula biliar asociados con la dificultad quirúrgica. MÉTODOS: Los pacientes que se sometieron tanto a MRI preoperatoria como a colecistectomía precoz por colecistitis aguda entre 2012 y 2018 fueron identificados retrospectivamente. En base a la distribución en capas de la pared de la vesícula biliar en la MRI, los pacientes se clasificaron en tres grupos: (1) intensidad de señal alta (high signal intensity, HSI), (2) intensidad de señal intermedia (intermediate signal intensity, ISI) y (3) intensidad de señal baja (low signal intensity, LSI). El objetivo final fue la presencia de cambios patológicos en la vesícula biliar asociados con la dificultad quirúrgica, tales como necrosis, formación de abscesos y fibrosis. RESULTADOS: De los 229 pacientes elegibles, se documentaron cambios patológicos asociados con dificultad quirúrgica en 17 (27,4%) de 62 pacientes en el grupo HSI, 84 (84,8%) de 99 pacientes en el grupo ISI y 66 (97,1%) de 68 pacientes en el grupo LSI (P < 0,001). Para detectar estos cambios, la intensidad de señal de intermedia a baja de la pared de la vesícula biliar tuvo una sensibilidad del 89,8% (i.c. del 95% 84,2%-94,0%), una especificidad del 72.6% (i.c. del 95% 59,8%-83,1%) y una precisión del 85,2% (i.c. del 95% 79,9%-89,5%). CONCLUSIÓN: La MRI preoperatoria predijo los cambios patológicos asociados con la dificultad quirúrgica durante la colecistectomía laparoscópica por colecistitis aguda.

Efficacy of dimethyl fumarate in Japanese multiple sclerosis patients: interim analysis of randomized, double-blind APEX study and its open-label extension.

BACKGROUND: Current data for the use of dimethyl fumarate (DMF) in Japanese patients with relapsing-remitting multiple sclerosis (RRMS) is limited. OBJECTIVES: To assess the efficacy of DMF in Japanese patients with RRMS. METHODS: The phase 3, multinational APEX study (ClinicalTrials.gov identifier: NCT01838668) consisted of two parts: a 24-week double-blind part where subjects were randomized to receive DMF 240 mg or placebo twice daily in East Asian and Eastern European countries, and an open-label extension part where all subjects received DMF. The primary endpoint was the total number of new gadolinium-enhancing lesions in Weeks 12-24. In this interim analysis, we report efficacy data in the Japanese subgroup (DMF n = 56; placebo n = 58) over 72 weeks, including an extension phase. RESULTS: DMF reduced the total number of new gadolinium-enhancing lesions in Weeks 12-24 by 85% versus placebo (p < 0.0001). At Week 24, the annualized relapse rate was also reduced by 48% with DMF, versus placebo. DMF reduced the probability of relapse from Week 8 and was sustained. The number of gadolinium-enhancing lesions was maintained through 72 weeks. CONCLUSIONS: DMF demonstrated sustained efficacy in this Japanese subgroup. The results were consistent with those observed in studies of DMF enrolling primarily Caucasian patients.

Randomized clinical trial of single skin sterilization with a povidone-iodine applicator versus conventional skin sterilization in abdominal surgery.

Background: The efficacy of widely used povidone-iodine applicators for skin sterilization in abdominal surgery is unclear. The aim of this trial was to evaluate whether sterilization with a povidone-iodine applicator was not inferior to a conventional sterilization method. Methods: Patients undergoing elective abdominal surgery were assigned randomly to receive single sterilization with the applicator or conventional sterilization. The primary endpoint was wound infection rate. Secondary endpoints were rate of organ/space surgical-site infection (SSI), adverse effects of povidone-iodine, amount of povidone-iodine used and total cost of sterilization. Results: Of 498 patients eligible for the study between April 2015 and September 2017, 240 were assigned and analysed in the applicator group and 246 in the conventional group. Wound infection was detected in 16 patients (6·7 per cent) in the applicator group and 16 (6·5 per cent) in the conventional group (absolute difference 0·0016 (90 per cent c.i. -0·037 to 0·040) per cent; P = 0·014 for non-inferiority). There was no difference between the groups in the organ/space SSI rate (11 patients (4·6 per cent) in the applicator group and 16 (6·5 per cent) in the conventional group. Both the amount of povidone-iodine used and the total cost of sterilization were higher in the conventional group than in the applicator group (median 76·7 versus 25 ml respectively, P < 0·001; median €7·0 versus €6·4, P < 0·001). Skin irritation was detected in three patients in the conventional group. Conclusion: In abdominal surgery, this povidone-iodine applicator was not inferior to conventional sterilization in terms of the wound infection rate, and it is cheaper. Registration number: UMIN000018231 (http://www.umin.ac.jp/ctr/).

Faecal freezing preservation period influences colonization ability for faecal microbiota transplantation.

AIMS: There has been growing interest in faecal microbiota transplantation (FMT) as treatment. Although, frozen donor faeces preserved at -20°C has been widely used for practical advantages, freezing at -20°C can affect bacterial viability. Adequacy evaluation of fresh and frozen faeces as the transplant is necessary for the methodological improvement of FMT. METHODS AND RESULTS: The viable bacterial compositions of faecal specimens under fresh and freezing conditions were compared by a microbiome analysis using propidium monoazide (PMA microbiome). In addition, recovery abilities from bacterial reduction by antibiotics were compared between fresh and frozen FMT using a murine model. PMA microbiome results suggested that freezing and freeze-thawing did not significantly affect in vitro faecal bacterial viability. However, the recovery effect from antimicrobial cleansing in frozen FMT was reduced in a freezing time-dependent manner, especially prominent in Actinobacteria and Bacteroidetes phyla. CONCLUSIONS: Short-term freezing preservation of faeces exhibited maintenance of enteric colonization ability in frozen FMT in comparison to 1 month -20°C-preservation. SIGNIFICANCE AND IMPACT OF THE STUDY: Long-term -20°C-preservation of transplanted faeces can result in instability of the clinical outcome in FMT therapy. The standardization of practical procedures of FMT therapy according to disease types is desirable.

Comparison between dexmedetomidine and midazolam as a sedation agent with local anesthesia in inguinal hernia repair: randomized controlled trial.

PURPOSE: In Japan, inguinal hernia repair is widely performed with local anesthesia. The objective of this study was to evaluate safety and efficacy of intravenous dexmedetomidine as a sedation agent with local anesthesia in inguinal hernia repair. METHODS: We performed this randomized, single-blind study for 200 patients who were scheduled to undergo inguinal hernia repair with local anesthesia. Patients were randomly divided into two groups (dexmedetomidine group: Group D, midazolam group: Group M). The primary outcome was to evaluate the safety of intravenous dexmedetomidine. Secondary outcomes were to analyze results of operators' surveys and patients' questionnaires and evaluate implementation of conscious sedation. RESULTS: Incidence of respiratory depression was significantly higher in Group M than Group D (p = 0.03). Other adverse events examined did not differ significantly. All three operators' questionnaires indicated that results were better in Group D than Group M. More than 70% of patients in both groups were satisfied with the surgery. More than 80% of Group D patients and 74% of Group M patients achieved a state of conscious sedation. CONCLUSION: This study demonstrated that intravenous dexmedetomidine during hernia repair with local anesthesia is safe and the results were satisfactory to both operators and patients.

Dynamics of L cells along the crypt-villous axis in the chicken ileum.

The dynamics of L cells along the crypt-villous axis were investigated in the ileum of male White Leghorn chicks (7 d of age, n = 5). Immunohistochemistry was used to detect the expression of glucagon-like peptide (GLP)-1 and an in situ hybridization technique to detect proglucagon messenger RNA (mRNA). Immunocytochemistry using colloidal gold was also applied to quantitatively evaluate the GLP-1 content. The cells expressing a proglucagon mRNA signal were distributed mainly in the crypts and the bottom of the villi but were never found in the upper part of the villi. Most of the cells expressing a proglucagon mRNA signal (97%) were immunoreactive for GLP-1 antiserum. In contrast, GLP-1 immunoreactive cells were distributed from the crypts to the middle part of the villi, and only 55% of them expressed a proglucagon mRNA signal. Quantitative evaluation by immunocytochemistry of GLP-1 using colloidal gold revealed that the GLP-1 content was significantly lower in L cells located in the villous epithelium than that of L cells located in the crypts (P < 0.01). These findings indicate that L cells in the chicken ileum mature and complete GLP-1 production in the crypts. L cells in the villous epithelium secrete GLP-1 but do not synthesize this peptide.

Early results of multicenter phase II trial of perioperative oxaliplatin and capecitabine without radiotherapy for high-risk rectal cancer: CORONA I study.

BACKGROUNDS: Perioperative introduction of developed chemotherapy into the treatment strategy for locally advanced rectal cancer (LARC) may be a promising option. However, the most prevalent treatment for high-risk LARC remains preoperative chemoradiotherapy (CRT) in Western countries. PATIENTS AND METHODS: A phase II trial was undertaken to evaluate safety and efficacy of perioperative XELOX without radiotherapy (RT) for patients with high-risk LARC. Patients received 4 cycles of XELOX before and after surgery, respectively. Primary endpoint was disease-free survival. RESULTS: We enrolled 41 patients between June 2012 and April 2014. The completion rate of the preoperative XELOX was 90.3%. Twenty-nine patients (70.7%) could start postoperative XELOX, 15 of these patients (51.7%) completed 4 cycles. Allergic reaction to oxaliplatin was experienced by 5 patients (17.2%) during postoperative XELOX. One patient received additional RT after preoperative XELOX. Consequently, the remaining 40 patients underwent primary resection. Major complications occurred in 6 of 40 patients (15.0%). Pathological complete response (pCR) rate was 12.2%, and good tumor regression was exhibited in 31.7%. N down-staging (cN+ to ypN0) and T down-staging were detected in 56.7% and 52.5%, respectively. Clinical T4 tumor was a predictor of poor pathological response (p < 0.001). CONCLUSIONS: We could show the favorable pCR rate after preoperative XELOX alone. However, the T and N down-staging rate was likely to be insufficient. When tumor regression is essential for curative resection, the use of preoperative CRT is likely to be recommended. For patients with massive LN metastasis, the additional Bev to NAC might be a promising option.

A case of trichilemmal carcinoma with distant metastases in a kidney transplantation patient.

Transplant recipients receiving immunosuppressants are at a high risk of cancer, especially skin cancer. Trichilemmal carcinoma is comparatively rare compared with other skin cancers. We report here a first case of trichilemmal carcinoma arising in a kidney transplant recipient. A 63-year-old man who had undergone a living donor renal transplantation at the age of 50 years presented with a 15 × 10 mm lesion on his forehead. The pathological diagnosis after resection was trichilemmal carcinoma. Distant metastases involving the lymph nodes, lung, and liver occurred, and the patient died. Given that trichilemmal carcinoma generally has an indolent clinical course and a low metastatic potential, the present case of trichilemmal carcinoma with an aggressive course resulting in distant metastases is rare.

Multi-drug-resistant Staphylococcus aureus and future chemotherapy.

Staphylococcus (S.) aureus silently stays as our natural flora, and yet sometimes threatens our life as a tenacious pathogen. In addition to its ability to outwit our immune system, its multi-drug resistance phenotype makes it one of the most intractable pathogenic bacteria in the history of antibiotic chemotherapy. It conquered practically all the antibiotics that have been developed since 1940s. In 1961, the first MRSA was found among S. aureus clinical isolates. Then MRSA prevailed throughout the world as a multi-resistant hospital pathogen. In 1997, MRSA strain Mu50 with reduced susceptibility to vancomycin was isolated. Vancomycin-intermediate S. aureus (VISA), so named according to the CLSI criteria, was the product of adaptive mutation of S. aureus against vancomycin that had long been the last resort to MRSA infection. Here, we describe the genetic basis for the remarkable ability of S. aureus to acquire multi-antibiotic resistance, and propose a novel paradigm for future chemotherapy against the multi-resistant pathogens.

A comparative study of thin-section CT findings between seasonal influenza virus pneumonia and Streptococcus pneumoniae pneumonia.

OBJECTIVE: To compare the pulmonary thin-section CT findings in patients with seasonal influenza virus pneumonia with Streptococcus pneumoniae pneumonia. METHODS: The study group included 30 patients (20 males and 10 females; age range, 20-91 years; mean age, 55.9 years) with seasonal influenza virus pneumonia and 71 patients (47 males and 24 females; age range, 27-92 years; mean age, 67.5 years) with S. pneumoniae pneumonia. RESULTS: The proportion of community-acquired infection was significantly higher in patients with influenza virus pneumonia than with S. pneumoniae pneumonia (p = 0.001). CT findings of ground-glass attenuation (GGA) (p = 0.012) and crazy-paving appearance (p = 0.03) were significantly more frequent in patients with influenza virus pneumonia than with S. pneumoniae pneumonia. Conversely, consolidation (p < 0.001), mucoid impaction (p < 0.001), centrilobular nodules (p = 0.04) and pleural effusion (p = 0.003) were significantly more frequent in patients with S. pneumoniae pneumonia than in those with influenza virus pneumonia. CONCLUSION: Pulmonary thin-section CT findings, such as consolidation and mucoid impaction may be useful in distinguishing between seasonal influenza virus pneumonia and S. pneumoniae pneumonia. ADVANCES IN KNOWLEDGE: (1) Distinguishing seasonal influenza virus pneumonia with S. pneumoniae pneumonia is important. (2) The CT findings of GGA and crazy-paving appearance were more frequently found in patients with influenza virus pneumonia than in patients with S. pneumoniae pneumonia, whereas consolidation, mucoid impaction, centrilobular nodules and pleural effusion were more frequently found in patients with S. pneumoniae pneumonia.

Construction and molecular characterization of a T-cell receptor-like antibody and CAR-T cells specific for minor histocompatibility antigen HA-1H.

The genetic transfer of T-cell receptors (TCRs) directed toward target antigens into T lymphocytes has been used to generate antitumor T cells efficiently without the need for the in vitro induction and expansion of T cells with cognate specificity. Alternatively, T cells have been gene-modified with a TCR-like antibody or chimeric antigen receptor (CAR). We show that immunization of HLA-A2 transgenic mice with tetramerized recombinant HLA-A2 incorporating HA-1 H minor histocompatibility antigen (mHag) peptides and ß2-microglobulin (HA-1 H/HLA-A2) generate highly specific antibodies. One single-chain variable region moiety (scFv) antibody, #131, demonstrated high affinity (KD=14.9 nM) for the HA-1 H/HLA-A2 complex. Primary human T cells transduced with #131 scFV coupled to CD28 transmembrane and CD3ζ domains were stained with HA-1 H/HLA-A2 tetramers slightly more intensely than a cytotoxic T lymphocyte (CTL) clone specific for endogenously HLA-A2- and HA-1 H-positive cells. Although #131 scFv CAR-T cells required >100-fold higher antigen density to exert cytotoxicity compared with the cognate CTL clone, they could produce inflammatory cytokines against cells expressing HLA-A2 and HA-1 H transgenes. These data implicate that T cells with high-affinity antigen receptors reduce the ability to lyse targets with low-density peptide/MHC complexes (~100 per cell), while they could respond at cytokine production level.

The influence of restricted feeding on glucagon-like peptide-1 (GLP-1)-containing cells in the chicken small intestine.

The influence of restricted feeding on the distribution of glucagon-like peptide-1 (GLP-1)-containing endocrine cells in the chicken small intestine was investigated using immunohistochemical and morphometrical techniques. This study demonstrated that the restricted feeding had an influence on the activity of GLP-1-immunoreactive cells in the chicken small intestine. There were differences in the localization and the frequency of occurrence of GLP-1-immunoreactive cells in the small intestine between control and restricted groups, especially 25% feed supply group provided with 25% of the intake during the adapting period. GLP-1-immunoreactive cells in the control chickens were mainly located in epithelium from crypts to the lower part of intestinal villi. Those in restricted groups, however, tended to be located from crypts to the middle part of intestinal villi. The frequency of occurrence of GLP-1-immunoreactive cells was lowest in the control group, medium in 50% feed supply group and highest in 25% feed supply group at each intestinal region examined in this study, that is, increased with the advancement of restricting the amount of feed supply. These data show that the quantity of food intake is one of signals that have an influence on the secretion of GLP-1 from L cells in the chicken small intestine.

Effect of the angiotensin II receptor antagonist olmesartan on morning home blood pressure in hypertension: HONEST study at 16 weeks.

Morning home blood pressure (BP) levels are more closely associated with cardiovascular risk than clinic BP levels. However, control of morning home BP has been worse than that of clinic BP in clinical practice. We examined the effects of olmesartan-based treatment using data (n=21 341) from the first 16 weeks of the Home BP measurement with Olmesartan Naive patients to Establish Standard Target blood pressure (HONEST) study, a prospective observational study for olmesartan-naive patients with essential hypertension. After 16-week olmesartan-based treatment, the clinic and morning home systolic BP (SBP) lowered from 151.6±16.4 and 153.6±19.0 mm Hg to 135.0±13.7 and 135.5±13.7 mm Hg, respectively (P<0.0001). The achievement percentage of target morning home SBP (<135 mm Hg) in all patients, those with diabetes mellitus (DM), and those with chronic kidney disease (CKD) increased from 13.5, 16.4 and 17.2% to 50.8, 47.9 and 48.8%, respectively, and the proportion of patients with well-controlled hypertension (clinic SBP<140 mm Hg and morning home SBP<135 mm Hg) increased from 7.9, 9.2 and 10.2% to 38.9, 34.5 and 36.3%, respectively. After 16-week olmesartan-based treatment, the proportion of patients with masked and white coat hypertension changed from 11.8 to 24.2% and 5.6 to 11.9%. In conclusion, both clinic and morning home BP in all, DM and CKD patients improved with 16-week olmesartan-based treatment in the 'real world', and the results showed a sustained 24-hour BP-lowering effect of olmesartan. Decrease in clinic and home BP resulted in an increased rate of masked and white coat hypertension, and further management is needed in those patients.

High-resolution CT findings in Streptococcus milleri pulmonary infection.

AIM: To assess pulmonary high-resolution computed tomography (CT) findings in patients with acute Streptococcus milleri pulmonary infection. MATERIALS AND METHODS: Sixty consecutive patients with acute S. milleri pneumonia who had undergone high-resolution CT chest examinations between January 2004 and March 2010 were retrospectively identified. Twenty-seven patients with concurrent infections were excluded. The final study group comprised 33 patients (25 men, 8 women; aged 20-88 years, mean 63.1 years) with S. milleri infection. The patients' clinical findings were assessed. Parenchymal abnormalities, enlarged lymph nodes, and pleural effusion were evaluated on high-resolution CT. RESULTS: Underlying conditions included malignancy (n = 15), a smoking habit (n = 11), and diabetes mellitus (n = 8). CT images of all patients showed abnormal findings, including ground-glass opacity (n = 24), bronchial wall thickening (n = 23), consolidation (n = 17), and cavities (n = 7). Pleural effusion was found in 18 patients, and complex pleural effusions were found in seven patients. CONCLUSION: Pulmonary infection caused by S. milleri was observed mostly in male patients with underlying conditions such as malignancy or a smoking habit. The CT findings in patients with S. milleri consisted mainly of ground-glass opacity, bronchial wall thickening, pleural effusions, and cavities.

Investigation of nasal meticillin-resistant Staphylococcus aureus carriage in a haemodialysis clinic in Japan.

Patients and healthcare workers in a Japanese haemodialysis clinic were investigated for nasal carriage of meticillin-resistant Staphylococcus aureus (MRSA). MRSA carriage was found in 10 (8.9%) of 112 patients in the first year and four (3.9%) of 103 patients in the second year. All isolated MRSA samples carried staphylococcal cassette chromosome mec type II or III and classified as clonal complex 5, which were common as healthcare-associated strains. Pulsed-field gel electrophoresis indicated horizontal transmission limited to two pairs of patients in one session. One of 54 healthcare workers carried MRSA genetically unrelated to patients' strains. Infection control measures based on the US Centers for Disease Control and Prevention's recommendation showed limited spread of MRSA in a haemodialysis room.

Mesenteric phlebosclerosis associated with long-term oral intake of geniposide, an ingredient of herbal medicine.

BACKGROUND: Idiopathic mesenteric phlebosclerosis (IMP) is a rare disease, characterised by thickening of the wall of the right hemicolon with calcification of mesenteric veins. However, the aetiology remains unknown. AIM: To investigate the possible association of herbal medicines with IMP. METHOD: The clinical data of four of our own patients were collected. Furthermore, we searched for previous reports about similar patients with detailed descriptions of herbal prescriptions that they had taken. We compared herbal ingredients to identify the toxic agent as a possible aetiological factor. RESULTS: Clinical data on a total of 25 patients were summarised. Mean age was 61.8 years and there was female predominance (6 men and 19 women). The used Kampo prescription, the number of cases, and the mean duration of use were as follows: kamisyoyosan in 12 cases for 12.8 years, inshin-iseihaito in 5 cases for 13.4 years, orengedokuto in 4 cases for 14.3 years, inchinkoto in 1 case for 20 years, kamikihitou in 1 case for 19 years, seijobofuto in 1 case for 10 years and gorinsan in 1 case for an unknown duration. Only one ingredient, sansisi, was common to the herbal medicines of all 25 patients. This crude drug called geniposide in English is a major constituent of the Gardenia fruits. CONCLUSION: The long-term use of geniposide in herbal medicines appears to be associated with mesenteric phlebosclerosis.

Inhibitory effect of statins on inflammatory cytokine production from human bronchial epithelial cells.

Statins are 3-hydroxy-3-methylglutaryl-co-enzyme A reductase inhibitors of cholesterol biosynthesis, and have been reported to exert pleiotropic effects on cellular signalling and cellular functions involved in inflammation. Recent reports have demonstrated that previous statin therapy reduced the risk of pneumonia or increased survival in patients with community-acquired pneumonia. However, the precise mechanisms responsible for these effects are unclear. In the present study, we examined the effects of statins on cytokine production from lipopolysaccharide (LPS)-stimulated human bronchial epithelial cells (BEAS-2B). Interleukin (IL)-6 and IL-8 mRNA expression and protein secretion in LPS-stimulated cells were inhibited significantly by the lipophilic statin pitavastatin and the hydrophilic statin pravastatin. As these inhibitory effects of statin were negated by adding mevalonate, the anti-inflammatory effects of statins appear to be exerted via the mevalonic cascade. In addition, the activation levels of Ras homologue gene family A (RhoA) in BEAS-2B cells cultured with pitavastatin were significantly lower than those without the statin. These results suggest that statins have anti-inflammatory effects by reducing cytokine production through inhibition of the mevalonic cascade followed by RhoA activation in the lung.

Prevalence of antiseptic-resistance genes in Staphylococcus aureus and coagulase-negative staphylococci colonising nurses and the general population in Hong Kong.

Reduced biocide susceptibility in staphylococci is associated with quaternary ammonium compound (qac) gene-encoding efflux proteins. This study compared the prevalence of antiseptic-resistance genes (qacA/B, smr) in staphylococci colonising nurses and non-healthcare workers. Staphylococcus aureus and coagulase-negative staphylococci (CoNS) isolated from 249 nurses were compared for qacA/B and smr positivity with carriage isolates from non-healthcare workers. Associations between qac genes and antibiotic resistance were investigated and minimum inhibitory concentrations (MICs)/minimum bactericidal concentrations (MBCs) to benzalkonium chloride and chlorhexidine determined. Both genes had higher prevalence in CoNS from nurses (OR: 8.4; 95% CI: 5.4-13.2) and qacA/B was more common in nurses'S. aureus isolates than those of the general population (OR: 5.5; 95% CI: 2.7-11.2). Meticillin-resistant S. aureus (MRSA) carriage was low (3.2% nurses; 0.5% general population). The risk of harbouring qacA/B and smr was associated with presence of mecA (OR: 2.9; 95% CI: 1.8-4.8) and contact with MRSA-infected patients (OR: 2.0; 95% CI: 1.0-3.9) in S. aureus and CoNS. S. aureus with qac genes displayed significantly more antibiotic resistance and all gene-positive isolates had higher MICs and MBCs to antiseptics. Increased prevalence of antiseptic-resistance genes in staphylococci from nurses indicates that the hospital environment could exert selective pressure for carriage of these strains. The increased proportion of qac genes in meticillin-resistant strains suggests co-selection of these genes, as does the increased carriage of gene-positive strains by those in contact with MRSA-positive patients. Reduced antiseptic susceptibility may allow persistence of organisms in the presence of low level residues and contribute to survival of MRSA.