Treatment of congenital cystic adenomatoid malformation-does resection in the early postnatal period increase surgical risk?

OBJECTIVE: The recent development of fetal ultrasonography has allowed for an increasing number of prenatal diagnoses for congenital cystic adenomatoid malformation (CCAM). However, the appropriate surgical timing of these patients has not been studied as of yet. The aim of this study is to suggest a safe strategy for the treatment of CCAM by identifying the relationship between the timing of surgery and postoperative outcome. METHODS: Between 1987 and 2003, 40 patients (28 males, 12 females) underwent surgical resection for CCAM. The mean age was 38.6+/-9.1 (2 days-13 years) months. CCAM was diagnosed by prenatal ultrasonography in eight patients. Early operations were performed in four out of the eight. Operation was deferred until 2-12 months of age for the remaining four patients. RESULTS: Type I CCAM was found in 20 patients, type II in 20 and no patient exhibited type III. Five patients had associated pectus excavatum anomaly. There were no cases of operative mortality. Seventeen minor postoperative complications developed in 16 patients (40.0%): prolonged chest tube drain in 10, wound infection in 4, and 1 case of pneumonia, empyema and pleural space, respectively. The average hospital stay was 11.8 (6-29) days. During the mean follow-up period of 67.5 months, one patient died of accidental aspiration 7 months after operation during the postoperative recovery course of Ravich operation for pectus excavatum. The remaining patients reported doing well with normal physical activity. All five patients who underwent surgery at the age of under 1 month did not exhibit increased postoperative morbidity. CONCLUSIONS: We concluded that surgery for CCAM could be safely performed in all age groups with satisfactory long-term outcomes. It is suggested that early elective surgical correction can be recommended for a patient whose diagnosis was made in utero.     

Thymidine labeling index in breast tumors

The relationship between primary tumor proliferative activity and clinical and pathologic characteristics was analyzed in relation to menopausal status in 32 patients with malignant or benign breast disease. The thymidine labeling index (TLI) showed significantly higher median values in the cancer patients (3.48 per cent) than in the patients with benign diseases (1.02 per cent). TLI was not significantly affected by delayed incubation at room temperature for about 1 hour. In the breast cancer patients, TLI did not significantly correlate to tumor size, the presence of axillary lymph node metastasis or pathologic nuclear grading. The only significant difference was limited to the breast cancer patients without axillary lymph node metastasis in relation to menopausal status; the TLI in the premenopausal patients (5.10 per cent) was significantly higher (p<0.05) than that in the postmenopausal patients (2.28 per cent). These data thus suggest that among premenopausal patients without axillary lymph node metastasis, those with a high TLI could be potential candidates for adjuvant chemotherapy.     

Intestinal bacterial metabolism of flavonoids and its relation to some biological activities

Flavonoid glycosides were metabolized to phenolic acids via aglycones by human intestinal microflora producing α-rhamnosidase, exo-β-glucosidase, endo-β-glucosidase and/or β-glucuronidase. Rutin, hesperidin, naringin and poncirin were transformed to their aglycones by the bacteria producing α-rhamnosidase and β-glucosidase or endo-β-glucosidase, and baicalin, puerarin and daidzin were transformed to their aglycones by the bacteria producing β-glucuronidase, C-glycosidase and β-glycosidase, respectively. Anti-platelet activity and cytotoxicity of the metabolites of flavonoid glycosides by human intestinal bacteria were more effective than those of the parental compounds. 3,4-Dihydroxyphenylacetic acid and 4-hydroxyl-phenylacetic acid were more effective than rutin and quercetin on anti-platelet aggregation activity. 2,4,6-Trihydroxybenzaldehyde, quercetin and ponciretin were more effective than rutin and ponciretin on the cytotoxicity for tumor cell lines. We insist that these flavonoid glycosides should be natural prodrugs.     

Bilateral versus unilateral sudden sensorineural hearing loss.

OBJECTIVES: To analyze the clinical characteristics and treatment results between bilateral (bi-) and unilateral (uni-) sudden sensorineural hearing loss (SSNHL). STUDY DESIGN AND SETTING: A retrospective study. METHODS: Three hundred twenty-four patients with SSNHL were classified into two groups; simultaneous bi-SSNHL (n = 16) and uni-SSNHL (n = 308). We compared clinical characteristics, medical history, hearing level, and treatment results between the 2 groups. RESULTS: The incidence of bi-SSNHL was 4.9 percent of overall patients with SSNHL. Bi-SSNHL occurs more commonly in patients of older age, with preexisting diabetes mellitus, and lipid panel abnormalities compared with uni-SSNHL. Ten patients (62.5%) in the bi-SSNHL group showed hearing recovery in 1 or both ears compared with 56.5 percent of patients with uni-SSNHL. Only 12 (37.5%) of all 32 ears recovered in bi-SSNHL, which was significantly lower than in uni-SSNHL. CONCLUSION: Bi-SSNHL has a very low incidence and lower recovery rate than uni-SSNHL. Recognition of similarities and differences between bilateral and unilateral SSNHL can help in counseling and managing the patients.     

Immunocytochemical localization of zinc transporter 3 in the ependyma of the mouse spinal cord

We report, for the first time, the light microscopical and ultrastructural appearance of ZnT3-immunoreactivities in the ependymal cells of the central canal of the mouse spinal cord. Light microscopy revealed the presence of ZnT3-immunoreactive (Ir) ependymal cells in 1 microm thick epon sections stained by the ABC method. The ZnT3-Ir cells were observed at all levels of the spinal cord, but were a little more numerous in lumbosacral segments than in cervicothoracic segments. The ZnT3-Ir cells had large, ovoid nuclei with abundant cytoplasm, and protruded into the lumen of the central canal. Our ultrastructural findings suggest that the ZnT3-Ir ependymal cells possess secretory activity directed towards the central canal. We propose that they may play a role in the trans-ependymal mechanism responsible for zinc homeostasis between cerebrospinal fluid and the central area of the gray matter.     

Combined effects of inhaled nitric oxide and a recruitment maneuver in patients with acute respiratory distress syndrome

Nitric oxide (NO) inhalation therapy has been employed in the management of acute respiratory distress syndrome (ARDS), in order to improve oxygenation. Several factors have been implicated as being responsible for the action of inhaled NO. Alveolar recruitment methods, such as prone positioning and a sufficient positive end expiratory pressure (PEEP), have been identified as having a positive impact on the NO response. A Recruitment maneuver (RM) was introduced for the treatment of ARDS, along with a lung protective strategy. Here, we hypothesized that a RM may further augment the oxygenation of patients treated with NO inhalation. Therefore, the effects of the inhalation of NO, either in combination with a RM, or separately, were evaluated on patients with ARDS for their enhancing action. 23 patients with ARDS were enrolled, and divided into three groups. The patients in group 1 (n=11) were treated with 5 ppm NO via inhalation, followed by a RM, applying a sustained inflation pressure of 30 - 35 cmH2O for 30 seconds. Group 2 (n=6) received a RM alone, while group 3 (n=3) was treated with NO inhalation alone. The oxygenation and hemodynamic parameters were obtained prior to, and 2, 12, and 24 h after, the respective treatment procedures. For group 1, the PaO2/FiO2 increased from its initial value of 171.8 +/- 67.8 to 203.2 +/- 90.0 2 h after NO inhalation. Further improvement was noted with the continual application of the RM reaching, 215.5 +/- 74.6 (p=0.05) and 254.2 +/- 109.5 (p < 0.05), after 12 and 24 h, respectively. Initially 7 of the subjects did not respond to NO inhalation, but 3 of these non-responders changed into responders 12 h after the RM. The changes in the PaO2/FiO2 from baseline at each time period were greater in group 1 than in the other groups, but with no statistical significance. The hemodynamics of the patients was not significantly altered during the entire study period. We conclude that the combined application of NO inhalation and a RM could be beneficial and safe for patients with ARDS, showing an enhancing effect in improvement of oxygenation.     

System for inducible expression of cre-recombinase from the Foxa2 locus in endoderm, notochord, and floor plate.

We targeted the reverse tetracycline controlled transactivator (rtTA) to the Foxa2 locus (Foxa2(ITA)) to generate a system for regulating Cre-recombinase activity within Foxa2 expression domains, including the endoderm, notochord, and floor plate of early mouse embryos. The use of an internal ribosomal entry site to obtain rtTA expression preserves Foxa2 function of the targeted allele. Cre activity with this system reflects the level of endogenous Foxa2 activity and is also tightly controlled by doxycycline. The location of Cre activity within the broader Foxa2 expression domain can be restricted by altering the timing of doxycycline administration. Isolated floor plate expression can be obtained in this manner. This system will provide a useful tool for manipulating gene expression in endoderm, notochord, and floor plate, all of which are tissues with important structural and patterning functions during embryogenesis.     

N(omega)-nitro-L-arginine methyl ester attenuates lithium-induced c-Fos, but not conditioned taste aversion, in rats

Lithium chloride (LiCl) at doses sufficient to induce conditioned taste aversion (CTA) causes c-Fos expression in the relevant brain regions and activates the hypothalamic-pituitary-adrenal (HPA) axis. It has been suggested that nitric oxide (NO) in the central nervous system may play a role not only in the activation of HPA axis but also in CTA learning, and that LiCl may activate the brain NO system. To determine the role of NO in lithium-induced CTA, we examined the lithium-induced CTA, brain c-Fos expression, and plasma corticosterone level with Nomega-nitro-L-arginine methyl ester (L-NAME) pretreatment. Intraperitoneal L-NAME (30 mg/kg) given 30 min prior to LiCl significantly decreased lithium-induced c-Fos expression in the brain regions implicated in CTA learning, such as the hypothalamic paraventricular nucleus (PVN), central nucleus of amygdala (CeA), and nucleus tractus of solitarius. However, either the lithium-induced CTA acquisition or the increase in plasma corticosterone was not attenuated by l-NAME pretreatment. These results suggest that NO may be involved in lithium-induced neuronal activation of the brain regions, but not in the CTA acquisition or the HPA axis activation.     

Methods for derivation of human embryonic stem cells

The expanded blastocysts, developed from 2PN-stage embryos, are generally divided into three categories: a good blastocyst containing a large and distinguishable inner cell mass (ICM), a blastocyst with a small and distinct ICM, and a blastocyst with a poorly defined ICM. In this study, we introduce methods for the derivation of human embryonic stem cells (hESCs) depending on the quality of the blastocysts. An immunosurgical method was used for the good expanded blastocysts. This method, however, raises the probability of ICM loss in cases of hESC derivation from blastocysts with smaller or indistinct ICMs. Furthermore, this method is also associated with a risk of the contamination of the hESCs with animal pathogens. To overcome these shortcomings, the partial- or whole-embryo culture method was used. For blastocysts with no visible ICM, the whole-embryo culture method was used to establish hESCs via the seeding of the entire blastocyst without its zona pellucida directly on a STO feeder layer. However, trophectodermal overgrowth tends to hinder the expansion of the ICM during the initial steps of hESC derivation. Therefore, the partial-embryo culture method was developed to establish hESCs from blastocysts with smaller ICMs. The surgical isolation of the region containing the ICM with an ultra-fine glass pipette alleviates trophectoderm overgrowth. This method is also applicable to blastocysts with large and distinct ICMs, and the efficiency of this method is comparable to that of the immunosurgical method.