The objective of this article is to investigate the clinical features of pulmonary metastasis (PM) from endometrial adenocarcinoma, in particular, the predictors of prolonged survival after PM detection. Fifteen patients who developed PM and underwent chest computed tomography (CT) scans for evaluation of PM were studied: 12 patients with pulmonary recurrence and 3 patients with PM on presentation. All patients with bilateral nodules or lymphangitic spread had metastases in other sites prior to or concomitant with PM, most of which were detected in para-aortic lymph nodes and/or the vaginal wall, while only one of five patients with a limited number (n < or = 5) of unilateral nodules had these metastases. The median survival time for the 10 patients with bilateral PMs was significantly shorter than that of the 5 patients with a limited number of unilateral nodules who were treated with surgery (7 versus 50 months, P = 0.005). Patients who developed pulmonary recurrence 2 years after the initial therapy had a significantly longer survival than those who developed it within 2 years (31 versus 10 months, P = 0.01). In conclusion, the distribution of PM determined by CT scans and the time interval between the initial therapy and the detection of pulmonary recurrence are the predictors of survival after PM detection.

Adenocarcinoma↗

PubMedDate not supplied

The effects of sarpogrelate on superoxide production by human neutrophils.

BACKGROUND AND OBJECTIVES: Superoxide anion (O2-) released from neutrophils plays an important role in antibacterial host defense system and tissue auto-injury. Sarpogrelate, a serotonin-receptor antagonist, has been successfully used for management of chronic pain caused by arterial occlusive or ischemic vascular diseases, or by microcirculation disturbances. Suppression of O2- generation may be detrimental to infection or contribute to the therapeutic approach to these diseases, the pathogenesis of which probably includes neutrophil activation. No data regarding the effects of sarpogrelate on neutrophil functions are available despite the possible clinical concern. The purpose of this study was to determine whether sarpogrelate reduces O2- production by human neutrophils using an in vitro system. In addition, we examined changes in concentrations of the intracellular calcium ion ([Ca2+]i), which is responsible for one of the mechanisms of the neutrophils' O2- production. METHODS: The O2- production by human neutrophils or the xanthine-xanthine oxidase system and [Ca2+]i were measured in the absence and the presence (at clinically relevant concentrations: 0.1x, 10x, and 100x these concentrations) of sarpogrelate. RESULTS: Sarpogrelate inhibited O2- production of neutrophils in a dose-dependent manner. The drug at a clinically relevant concentration suppressed this neutrophil function. In contrast, sarpogrelate failed to inhibit O2-generation by the cell-free (xanthine-xanthine oxidase) system. Elevation of [Ca2+]i in neutrophils stimulated by a chemotactic factor was dose-dependently attenuated with sarpogrelate. CONCLUSIONS: These findings suggest that sarpogrelate (even at clinically relevant concentrations) is able to inhibit O2- production by neutrophils. However, the drug failed to quench an excessive amount of O2- (similar to the level produced by neutrophils). There is a possibility that the inhibitory effect of the drug on [Ca2+]i response in neutrophils may contribute to impairment of the neutrophils' O2- production. Further studies using in vivo systems are required to elucidate the inhibitory effects of sarpogrelate on O2- in clinical settings.

Calcium↗

PubMedDate not supplied

Normal Y sequences in Smith-Lemli-Opitz syndrome with total failure of masculinization.

We report an infant with characteristics of Smith-Lemli-Opitz syndrome who had anteverted nostrils, apparently low-set ears, micrognathia, high-arched palate, cleft palate, growth and psychomotor retardation, hypotonia, poor suck, cerebral hypotrophy and double renal pelvis and ureter. An EEG showed spike waves in the right temporal area. The patient appeared to have normal internal and external genitalia of the female type. Both ovaries were dysplastic. The karyotype was 46,XY. All of 26 loci on the Y chromosome were positive including SRY, a candidate gene for TDF.

Abnormalities, Multiple↗

PubMedDate not supplied

Neutrophil chemotaxis, phagocytosis, and generation of reaction oxygen species show a hierarchy of responsiveness to increasing concentrations of N-formyl-Met-Leu-Phe.

We assessed the effect of varying concentrations of N-formyl-methionyl-leucyl-phenylalanine (fMLP) on neutrophil chemotaxis, phagocytosis, and reactive oxygen species generation. Boyden chamber chemotaxis was first elicited at an fMLP concentration of 10(-11) M, reached a peak at 10(-10) M, and declined at higher concentrations. Phagocytosis was first activated at 10(-10) M, reached its highest level at 10(-9) M, and declined at higher concentrations. O2-, H2O2 and OH. generation were elicited to a significant degree only at a fMLP concentration of 10(-8) M, or higher, reaching a peak at 10(-6) M. Thus, a distinct hierarchy was observed in the order of activation of these three neutrophil functions to varying concentrations of a soluble agonist. A teleologic model of neutrophil function that accounts for these observations is proposed.

Adolescent↗

PubMedDate not supplied

Inhibitory effect of gabexate mesilate on human neutrophil function.

Neutrophils accumulated in the lung are thought to play a key role in the pathogenesis of adult respiratory distress syndrome and interstitial pneumonia following bone-marrow transplantation. The effects of gabexate mesilate on several aspects of human neutrophil function have been investigated. Gabexate mesilate significantly decreased both the generation of reactive oxygen species (O2-, H2O2, OH.) by neutrophils and neutrophil chemotaxis. In contrast, the drug did not affect the levels of reactive oxygen species generated by a cell-free reactive-oxygen-species generating system. Intracellular calcium concentrations in neutrophils stimulated by f-Met-Leu-Phe were decreased in the presence of gabexate mesilate. These data suggest that the reduction in reactive-oxygen-species production and neutrophil chemotaxis by gabexate mesilate may contribute to the effectiveness of the drug in adult respiratory distress syndrome and interstitial pneumonia after bone-marrow transplantation. The suppression of the increase in intracellular calcium concentration may at least be responsible for the inhibition of these neutrophil functions by gabexate mesilate.

Calcium↗

PubMedDate not supplied

Acceleration of phagocytosis in human neutrophils incubated with gabexate mesilate.

It has recently been shown that gabexate mesilate inhibited human neutrophil functions including chemotaxis and reactive oxygen species production. In the present study, the effects of gabexate mesilate on phagocytosis by human neutrophils in vitro were investigated. Gabexate mesilate significantly enhanced neutrophil phagocytosis in a dose-dependent manner. This characteristic of gabexate mesilate may facilitate protection against infecting micro-organisms, although the inhibition of reactive oxygen species production by neutrophils may be a disadvantage for host-defense against infection.

Analysis of Variance↗

PubMedDate not supplied

Effect of nadifloxacin on neutrophil functions.

Recent reports indicate that nadifloxacin is an effective therapy for acne vulgaris and has a mechanism of action similar to that of the tetracyclines which act directly as antioxidants against infiltrated neutrophils. The effects of nadifloxacin on neutrophil functions, including the generation of reactive oxygen species, chemotaxis and phagocytosis were investigated. Nadifloxacin reduced the numbers of superoxide radical anions (O2-) and hydroxyl radicals (OH.) generated by neutrophils. The drug did not, however, significantly inhibit neutrophil chemotaxis and phagocytosis nor did it decrease the levels generated in a cell-free, xanthine-xanthine oxidase system. These results indicate that the clinical effectiveness of nadifloxacin may be partly due to its inhibitory action on the generation of O2- and OH. by neutrophils leading to a reduction in oxidative tissue injury.

Anti-Infective Agents↗

PubMedDate not supplied

Sensitivity of Staphylococcus aureus, isolated from skin infections in 1994, to 19 antimicrobial agents.

The most common pathogen causing skin infections is Staphylococcus aureus and the incidence of multiply resistant strains of S. aureus has been increasing. The in vitro susceptibility of 130 isolates of S. aureus to 19 antimicrobial agents: ampicillin (ABPC), methicillin, cefaclor, cefpodoxime proxetil, gentamicin, erythromycin, clindamycin, minocycline, vancomycin, fusidic acid, norfloxacin, ofloxacin, enoxacin, ciprofloxacin, lomefloxacin, tosufloxacin, sparfloxacin, nadifloxacin and grepafloxacin, was evaluated by agar dilution tests. The S. aureus isolates were isolated from 130 patients with skin infections in 1994. The proportion of methicillin-resistant S. aureus isolates among the strains isolated was 19.2%. The concentration needed to inhibit 50% of the isolates was 3.13 mg/ml or less for all of the drugs, but the concentration needed to inhibit 90% of isolates was over 12.5 micrograms/ml, except in the cases of minocycline, vancomycin, fusidic acid, tosufloxacin and nadifloxacin. Tosufloxacin and nadifloxacin had the lowest minimum inhibitory concentrations. None of the S. aureus strains was resistant to nadifloxacin.

Anti-Bacterial Agents↗

PubMedDate not supplied

Activity of nadifloxacin against methicillin-resistant Staphylococcus aureus isolated from skin infections: comparative study with seven other fluoroquinolones.

The in vitro susceptibility of methicillin-resistant Staphylococcus aureus (MRSA) to nadifloxacin and seven other fluoroquinolones (norfloxacin, ofloxacin, enoxacin, ciprofloxacin, lomefloxacin, tosufloxacin and sparfloxacin) was evaluated. The MRSA isolates were isolated from 114 skin infections between 1991 and 1994. Nadifloxacin exhibited the lowest minimum inhibitory concentration and there were no MRSA isolates resistant to nadifloxacin, while there were some resistant to all of the other seven fluoroquinolones. The minimum concentrations of these drugs needed to cause 50% inhibition of the isolates increased dramatically from 1991 to 1992, but has hardly changed since 1992.

Anti-Infective Agents↗

PubMedDate not supplied

The effect of roxithromycin on the generation of reactive oxygen species in vitro.

The effect of roxithromycin (ROM), a new oral semi-synthetic macrolide, on the generation of reactive oxygen species (ROS), using human neutrophils and a cell-free, xanthine-xanthine oxidase system was examined. The species investigated were the superoxide radical anion (O2-), hydrogen peroxide (H2O2), and the hydroxyl radical (OH.). ROM effectively inhibited the generation of O2-, H2O2 and OH. by human neutrophils. On the other hand, the drug did not markedly affect the ROS levels generated in the xanthine-xanthine oxidase system. The present study indicates that ROM may exert an anti-inflammatory action by inhibiting neutrophil oxygen radical generation at the sites of inflammation.

Anti-Bacterial Agents↗

PubMedDate not supplied

A novel enzymatic assay for the quantification of skin surface lipids.

The applicability of a novel enzymatic assay for quantifying skin surface lipids was investigated experimentally. The standard curves for the assays of glycerol esters, free fatty acids, and cholesterol and its esters were linear over a wide range of lipid concentrations, which ensures the accuracy of measurements. The assay system also showed good simultaneous reproducibility. There were significant positive correlations (P < 0.001) between the quantities of glycerol esters, free fatty acids, and cholesterol and its esters sampled from the skin surface of women when measured by the enzymatic assay compared with the gas chromatographic method. The enzymatic assay was applied to studies of the relationships between age, acne and menstrual cycle, and skin surface lipids in women. The quantities of glycerol esters and free fatty acids reached peaks in females in their twenties and thirties. Increased quantities of glycerol esters, free fatty acids, and cholesterol and its esters were observed in women with acne compared with women without acne. Among the women with acne, those in the premenstrual phase of the menstrual cycle showed increased levels of glycerol esters, free fatty acids, and cholesterol and its esters compared with those in the menstrual phase. The results suggest that the enzymatic method is a satisfactory new technique for the quantification of skin surface lipids.

Acne Vulgaris↗