Comparison of species, virulence genes and clones of Aeromonas isolates from clinical specimens and well water in Okinawa Prefecture, Japan.

AIMS: To reveal the sources of Aeromonas infection in Okinawa Prefecture of Japan, the species, virulence genes and clones of strains isolated from clinical specimens and well water were compared. METHODS AND RESULTS: The properties of both isolates were investigated by sequencing of rpoD, detection of 10 virulence genes using PCR and genotyping with pulsed-field gel electrophoresis. In all, 68 clinical and 146 well water strains of Aeromonas were isolated and the main species were A. caviae, A. dhakensis, A. hydrophila and A. veronii biovar sobria. Aeromonas dhakensis possessed various virulence genes; however, A. caviae possessed only fla. The same or similar clones were distributed in certain areas of Okinawa and one clone had survived several months in the biliary system of two patients, respectively. CONCLUSION: Although the same Aeromonas clone was not isolated from clinical and well water samples, our study revealed the detected patterns of virulence genes in both isolates, the distribution of identical/similar clones in the Okinawan environment and long-time survival in patient's organs. SIGNIFICANCE AND IMPACT OF THE STUDY: We investigated the association between Aeromonas patients and well water exposure. This study provides the properties of species, virulence genes and clones of Aeromonas isolated from samples of these origins.

Cost-effectiveness of palbociclib in hormone receptor-positive advanced breast cancer.

BACKGROUND: Palbociclib (PAL), a novel small-molecule inhibitor of cyclin-dependent kinases 4 and 6 for the treatment of advanced breast cancer, has demonstrated significant efficacy in prolonging progression-free survival when added to existing therapies. Considering the high cost of PAL, we assessed cost-effectiveness of adding PAL to usual care in treatment of advanced breast cancer. METHODS: We developed a discrete event simulation model to simulate time to cancer progression and to compare life time clinical benefit and cost of alternative treatment strategies for patients with metastatic disease from societal perspective. Per approved indication, endocrine treatment naive patients were assigned to PAL plus letrozole (PAL + LET) or letrozole alone (LET). Patients with prior endocrine therapy were assigned to PAL plus fulvestrant (FUL) (PAL + FUL) or FUL alone. The model assumptions were informed based on published clinical trial data and other peer reviewed studies. We carried out one-way and probabilistic sensitivity analyses to assess the robustness of our results to the changes in model assumptions. RESULTS: In treatment-naive patients, the addition of PAL to LET cost an estimated $768 498 per additional quality-adjusted life-year (QALY) gained. The addition of PAL to FUL in patients with prior endocrine therapy cost an estimated $918 166 per QALY gained. Sensitivity analyses demonstrated adding PAL has a 0% chance of being cost-effectiveness in either patient groups at a willingness-to-pay threshold of $100 000 per QALY. CONCLUSION: From a societal perspective, PAL treatment of both patient groups (with and without prior endocrine therapy) is highly unlikely to be cost-effective compared with the usual care in the USA.

Angioplasty with stenting is effective in treating blue toe syndrome.

Blue toe syndrome is a manifestation of distal embolization associated with significant pain and risk of tissue loss. The recommended treatment options for this problem include endarterectomy or bypass with exclusion of the source of emboli. Although focal arterial stenosis can be effectively treated with angioplasty,it is unclear whether performing angioplasty in a lesion suspected of causing distal embolization might actually worsen the condition or what long-term effects this would have in preventing future embolization. The purpose of this study was to evaluate the treatment and outcome of a series of patients with unilateral blue toe syndrome treated with percutaneous angioplasty and stenting. During a 5-year period, a total of 8 patients were identified with unilateral blue toe syndrome. Ankle/brachial indices (ABIs) were obtained, followed by arteriography. The study group included 4 men and 4 women with an age range of 35 to 83 years. Their atherosclerotic risk factors included smoking (8), hypertension (5), diabetes mellitus (3), and hypercholesterolemia (1). One patient had a history of illicit drug use. The patients were followed up by repeat clinical examinations and vascular laboratory studies. Arteriography typically demonstrated a focal preocclusive lesion with thrombus at the distal end of the lesion. Angioplasty and stent placement was technically successful in all cases. The ABIs increased following angioplasty (before 0.81 +/- 0.05; after 1.02 +/-.05). The symptoms resolved in all 8 patients over the ensuing month, and there were no recurrences with a mean follow-up of 18.5 months (range 4 to 36 months). There was 1 death at 4 months associated with preexisting colon carcinoma. Unilateral arterial to arterial emboli were found in association with focal preocclusive lesions. Despite the presence of thrombus in some of the lesions, these patients were not acutely worse following angioplasty. There was good initial angiographic success in all cases. There was also hemodynamic improvement as shown by the increased ankle/brachial indices. Although long-term follow-up is not available, these intermediate results suggest that angioplasty and stenting should be considered a reasonable alternative to standard operative approaches for patients with blue to syndrome associated with embolization from a focal stenosis.

Difference in hydrophobicity between botulinum type B activated and non-activated neurotoxins under low pH conditions.

We showed that botulinum type B activated neurotoxin with a di-chain structure became hydrophobic more quickly and extensively than did the non-activated toxin with a single-chain structure on low pH exposure. The activated toxin possessed 50-fold higher toxicity than did the non-activated type. The difference in the susceptibility to hydrophobic change may be one clue to answering the question of why the activated toxin possesses a higher toxicity than does the non-activated type.

Is there a role for routine mediastinoscopy in patients with peripheral T1 lung cancers?

BACKGROUND: The role of surgical staging of patients with non-small cell lung cancer (NSCLC) continues to evolve. This report describes our findings utilizing routine cervical mediastinoscopy in the evaluation of peripheral T1 (<3 cm) lung tumors. METHODS: Retrospectively 30 patients with peripheral T1 lesions and CT scans negative for pathologic adenopathy were identified over a 3-year period. Cervical mediastinoscopy was performed prior to VATS/thoracotomy during the same operative session. RESULTS: Mediastinoscopy was performed in 29 of 30 patients. For patients with malignancy (27 of 30), 3 of 27 (11%) had mediastinoscopy positive for malignancy and no further resection performed. Overall the subgroup of patients with bronchogenic carcinomas had positive mediastinal involvement identified in 5 of 24 (21%) after mediastinoscopy or complete resection. CONCLUSION: A significant number of patients with small peripheral lung cancers harbor radiographically occult lymph node involvement. Mediastinoscopy facilitates identification of patients with regionally advanced disease prior to resection, allowing neoadjuvant therapy and avoiding unnecessary resections.

[Gonadal dysfunction].

Function of hypothalamic-pituitary-ovarian axis is an essential factor for the maintenance of regular cycles in mature women. The disturbance of function of those organs causes gonadal dysfunction such as anovulation, amenorrhea and menstrual disorders. Therefore, the correct diagnosis for the assessment of CNS and ovarian function is clinically important to treat the patients those who have an menstrual disorders. In this review, the mechanism of normal gonadal cycles and the diagnostic method and the treatment of gonadal dysfunction are described.

[Stage IIIa endometrial carcinoma: MR findings].

[PURPOSE]: An attempt was made to evaluate the ability of magnetic resonance (MR) imaging to diagnose stage IIIa endometrial carcinoma. [MATERIALS AND METHODS]: Thirty-three patients with endometrial carcinoma underwent MR imaging and surgery. Surgical staging was classified as I in 21 patients, II in 3 patients and III in 9 patients. The MR images of each patient were retrospectively reviewed by three radiologists. Only the clinical diagnosis of endometrial carcinoma was previously notified. Segmental disruption of the full thickness of the myometrium was considered serosal invasion. Intraperitoneal metastasis was diagnosed according to three criteria (intraperitoneal solid mass of isointensity compared with endometrial lesion, cystic mass excluding benign ovarian cysts, ascites). These evaluations were compared with the surgical findings and analyzed by the kappa statistic. [RESULTS]: The rates of sensitivity and positive predictive value (PPV) for serosal invasion were 33% and 6%, respectively. False positive evaluation frequently occurred when thickness of the intact myometrium was less than 5mm. The rates of sensitivity and PPV for intraperitoneal metastasis were 86% and 72%, respectively. The reason for false negative evaluation was small foci of intraperitoneal metastasis. Overall, sensitivity and PPV for stage IIIa were 86% and 69%, respectively. [CONCLUSION]: MRI was useful in detecting intraperitoneal metastasis of endometrial carcinoma with the exception of diagnosing serosal invasion. It is difficult to detect small foci of peritoneal metastasis. It is necessary to differentiate adnexal metastasis from benign adnexal masses.

Effect of dehydroepiandrosterone sulphate, oestrogens and prostaglandins on collagen metabolism in human cervical tissue in relation to cervical ripening.

To clarify the mechanism of cervical ripening at term, collagenase activity in human cervical tissue was studied. The effects of steroids and prostaglandins on collagenase activity were also examined. Collagenase activities in cervical tissues obtained from non-pregnant (n = 5) and pregnant women (early-pregnant, n = 3; late-pregnant, n = 14) were measured, with or without the addition of steroids and prostaglandins into the incubation medium prior to the measurement of enzyme activity. The enzyme activity was significantly (P < 0.01-0.05) higher in the cervical tissue obtained from late-pregnant women than that from non-pregnant and early-pregnant women. Collagenase activity was significantly (P < 0.05) elevated when steroid sulphates such as dehydroepiandrosterone sulphate and oestrone sulphate were added to the incubation medium, while the addition of free steroids, prostaglandin E2 and prostaglandin F2 alpha did not alter the activity. These data suggest that conjugated steroid produced in the foetoplacental unit during pregnancy may be involved in cervical ripening through the enhancement of collagenase activity.

Determination of a new calcium antagonist, sesamodil fumarate (SD-3211), and its metabolite in plasma by liquid chromatography with electrochemical detection.

A sensitive and selective high-performance liquid chromatographic method is described for the determination of a novel calcium antagonist, (+)-(R)-3,4-dihydro-2-[5-methoxy-2-[3-[N-methyl-N-[2-[(3,4- methylenedioxy)phenoxy]ethyl]amino]propoxy]phenyl]-4-methyl-3-oxo-2H- 1,4-benzothiazine hydrogen fumarate (sesamodil fumarate; JAN, SD-3211, I), and its N-desmethylated metabolite (II) in plasma. Compounds I and II and an internal standard were isolated from plasma by solid-phase and liquid-liquid extraction. The extract was chromatographed on a reversed-phase C18 column, and the compounds of interest were detected by dual coulometric electrodes operated in an oxidative screen mode. The limit of determination for both I and II was at least 0.4 ng/ml in plasma. The utility of the assay was demonstrated by determining plasma levels of I and II in five dogs administered an oral dose of 60 mg of the drug.

Steroid concentrations in human cervical tissue in relation to cervical ripening.

Steroid concentrations in human cervical tissue were measured in order to study the mechanism of cervical ripening at term. Thirty-four women at 37 to 41 weeks of gestation were selected for the study and divided into two groups. Group A consisted of 21 cases with ripened cervix, and Group B consisted of 13 cases with non-ripened cervix. The condition of the cervix was judged by the Bishop's Score. Free and conjugated estrone (E1), estradiol (E2), estriol (E3), and dehydroepiandrosterone (DHA) concentrations in cervical tissue were measured by radioimmunoassay (RIA). Significantly higher concentrations of free E1, conjugated E2, E3 and DHA were found in Group A than in Group B. Cervical tissue during labor showed a further increase in the concentrations of these steroids. Pronounced increases of the steroid concentrations were noted following DHA-Sulfate (DHA-S) administration. These results suggest an intimate relationship between cervical ripening and steroid concentrations in cervical tissue during pregnancy.

Enhancement of human amniotic phospholipase A2 activity by steroid-sulphate derived from the foeto-placental unit.

To study the control of production of prostaglandins (PG) during pregnancy and parturition, amniotic membranes obtained from normal vaginal delivery were incubated with the substrate of phosphatidylcholine containing [14C]arachidonic acid in the Sn-2 position. Phospholipase A2 activity was calculated as the rate of release of [14C]arachidonic acid from the substrate. Various steroids were added to the incubation medium to elucidate the effect of steroids on the enzymatic activity. The addition of dehydroepiandrosterone-sulphate (DHA-sulphate) to the medium increased by 7-fold the rate of [14C]arachidonic acid release from phosphatidylcholine at a concentration of 1.67 mM. The enhanced rate of arachidonic acid release suggests that DHA-sulphate stimulates phospholipase A2 activity. The same amounts of pregnenolone-sulphate and oestrone-sulphate also enhanced the enzymatic activity, while cholesterol-sulphate, free steroids such as DHA, progesterone, cortisol and oestrogens revealed no effect. These results suggest that steroid sulphates may be involved in the regulatory mechanism for PG synthesis in amniotic membrane.

Simple assay of estrogen in urine during pregnancy by means of latex agglutination inhibition reaction.

A simple and rapid method, latex agglutination inhibition reaction (LAIR), using anti-estriol-16-glucuronide coupled with BSA for estimating estrogen in urine has been developed. Agglutination of the latex reagent by the antiserum occurs within 3 min. The agglutination, however, was completely inhibited by 100 ng/ml or more of estriol. There was a good correlation in results obtained by LAIR and by colorimetry, RIA and GLC. Urine samples (3329) obtained at various gestational weeks were assayed. The samples from 94% of the normal pregnant patients in the third trimester revealed 10 micrograms/ml or more of estrogens. Although the assay is semiquantitative, it may be useful in screening for fetal well-being in high-risk pregnancies.