Prenatal course and pregnancy outcome of fetuses with a transient nuchal translucency.

OBJECTIVES: This study was designed to correlate fetuses in a normal prenatal population who exhibited transient nuchal translucency (NT) with both prenatal course and pregnancy outcome. METHODS: The fetuses with abnormal NT were followed by ultrasonography at 1-2-week intervals during their prenatal course. Fetuses with NT who exhibited no detectable congenital malformations were defined as the NTO group; fetuses with abnormal NT and structural malformations but no chromosomal abnormalities were placed in the SM group; and fetuses with abnormal NT, structural malformations, and chromosomal abnormalities were categorized as the CA group. The groups were compared by: maternal age, weeks of gestation by ultrasound and the NT value at the initial exam, the maximum NT value, and the duration of abnormal NT. RESULTS: During the study period, 92 fetuses with abnormal NT were found, monochorionic twins excluded. Of the 92 fetuses, 80 were in the NTO group, 10 were in the SM group, and two were in the CA group. The maternal age and the gestational weeks at the initial diagnosis were not significantly different in the NTO and the SM groups. However, the NT value at the initial diagnosis, maximum NT value, and the duration of abnormal NT were significantly greater in the SM group than those values in the NTO group. CONCLUSIONS: Fetuses with transient nuchal translucency commonly had structural malformations, particularly fetuses with significant and large persistent NT.

Breast-conserving therapy for ductal carcinoma in situ.

This retrospective analysis evaluates the treatment results and prognostic factors of 114 patients with ductal carcinoma in situ (DCIS) undergoing breast conserving therapy (BCT) at Keio University Hospital Department of Radiology, between 1988 and 1997. A total of 132 patients with DCIS of the breast came to our hospital between 1988 and 1997, and 114 cases were suitable candidates for BCT. All of the patients were female and ranged in age from 26 to 81 years (median 46). Ninety-one patients were premenopausal, and 23 were postmenopausal. Median clinical tumor size was 2.0 cm (0-8.0 cm). Postoperatively 48 cases received 50 Gy/25 fractions of external irradiation to the whole breast via tangential ports. The follow-up period after treatment ranged from 11 to 162 months (median 46.7). The local relapse-free rate and overall survival rate of the 114 patients were 89.5% and 100%, respectively. Local failure and regional nodal failure occurred in 12 and 1 patient, respectively. Radiotherapy was a significant risk factor for local failure (p=0.05). No postmenopausal patients developed local failure, but the difference did not reach statistical significance (p=0.103). The 12 recurrent cases underwent additional surgery and all remain alive without recurrence, to date, i.e., at least 16 months. Breast-conserving surgery plus irradiation is appropriate treatment for DCIS patients.

Minimally invasive surgery for lung cancer with coronary artery disease.

We report a 69-year-old woman with lung cancer and severe stenosis in the left anterior descending coronary artery. To perform a curative operation for the lung cancer without myocardial infarction, minimally invasive direct coronary artery bypass and left lower lobectomy with video-endoscopic assistance were performed simultaneously. There was no major complication, and she was discharged at 14 days after the operation. This procedure may be useful and safe for patients with lung cancer and coronary artery disease.

Minimally invasive removal of infected pacemaker lead.

A 37-year-old woman with sick sinus syndrome suffered complications with recurring local infection at the generator pocket. Repeated debridement and antibiotic therapy was ineffective. Several attempts to remove leads via the implantation vein by direct traction were unsuccessful. We operated using cardiopulmonary bypass and applied a minimally invasive lower ministernotomy to obtain pleasing cosmetic results. After a right atriotomy, leads were removed. The minimally invasive approach gave satisfactory results, especially cosmetically.

Stress responses during laparoscopy with CO2 insufflation and with mechanical elevation of the abdominal wall.

STUDY OBJECTIVE: To compare the intensity of stress responses caused by laparoscopy combined with CO2 insufflation (CI) with those caused by mechanical elevation of the abdominal wall (MEA). DESIGN: Prospective study (Canadian Task Force classification I). SETTING: Tertiary care university hospital. PATIENTS: Thirty-one women. Intervention. Laparoscopy, 16 with CI and 15 with MEA. MEASUREMENTS AND MAIN RESULTS: Circulating levels of norepinephrine, epinephrine, cortisol, and interleukin (IL)-6 were compared in the two groups. Arterial partial pressure of CO2 (PaCO2) did not increase during laparoscopy by either method. Plasma norepinephrine and epinephrine levels increased after extubation in the MEA group but not in the CI group. Circulating cortisol levels in both groups increased during laparoscopy; mean intraoperative levels were higher in the CI group. Serum IL-6 levels increased after extubation in the MEA but not the CI group. Mean heart rate increased during laparoscopy in both groups, whereas blood pressure increased only in the CI group. More patients in the MEA group required postoperative analgesia. CONCLUSION: Laparoscopy with MEA caused more pronounced adrenosympathetic and cytokine responses than that with CI when PaCO2 was maintained within the range of normocapnia.

Melatonin secretion from organ-cultured pineal glands of rats: modulation by gonadectomy and gonadotropin-releasing hormone agonist administration.

The objective of the study was to evaluate the effect of pretreatments such as gonadectomy in male and female rats, and gonadotropin-releasing hormone agonist (GnRHa) administration in female rats, on levels of secretion of melatonin, using an organ culture of pineal glands. Gonadectomy 2 weeks before the animal was killed increased the amount of melatonin secreted into the medium by the pineal glands of female rats but not of male rats. The increase in in vitro melatonin secretion after ovariectomy in female rats was prevented by estrogen replacement. Ovariectomy 3 and 4 weeks before death also significantly increased the amount of melatonin secretion. Administration of GnRHa 2 weeks before decapitation significantly decreased serum estradiol concentrations and significantly increased melatonin secretion by the pineal glands of female rat. GnRHa administration 3 or 4 weeks before decapitation also significantly decreased serum estradiol concentrations, but did not increase pineal secretion of melatonin. The results indicate that ovariectomy increases melatonin secretion from organ-cultured pineal glands and that this increase is suppressed by estrogen in adult female rats. In contrast, orchiectomy in male rats does not influence in vitro secretion of melatonin. These results suggest that the GnRH-gonadotropin system may participate in the regulation of pineal melatonin secretion in adult female rats.

The modified tangential irradiation technique for breast cancer: how to cover the entire axillary region.

PURPOSE: The two-portal tangential irradiation technique has usually been applied to breast cancer patients after breast-conserving surgery (1, 2) and is expected to irradiate the axillary lymph node region to some extent (3). We investigated the range of the axillary region covered by this technique and tried to devise an optimal irradiation technique (modified tangential irradiation) that would cover the axillary lymph node region properly. METHODS AND MATERIALS: We checked the status of the surgical clips left at axillary lymph node sites by reviewing the simulator films and planning CT scans of 63 patients who underwent axillary dissection of level I, I-II, or I-III lymph nodes. Then we created the modified tangential irradiation technique and applied this technique to 16 patients and checked the irradiation volume by CT scans. RESULTS: We found that all of the surgical clips on lateral-view simulator films were on the ventral side of the dorsal edge line of the humeral head. All but one clip were on the caudal side of the caudal edge line of the humeral head. Accordingly, it is possible to irradiate almost all axillary lymph node regions by setting the dorsal edge of the irradiation field on lateral-view simulator films at the dorsal edge of the humeral head and the cranial edge at the caudal edge of the humeral head. CONCLUSIONS: All breast tissue and the entire axillary lymph node region can be covered by the modified tangential irradiation technique without increasing the lung volume irradiated.

The effect of melatonin on in vitro fertilization and embryo development in mice.

To examine the effect of melatonin on in vitro fertilization and embryonic development, mouse embryos after insemination in vitro were cultured in a physiological medium with or without melatonin. Melatonin increased the fertilization rate significantly at a concentration between 10(-6) and 10(-4) M (27.6 vs. 43.9 or 40.4%, P < 0.01). Furthermore, a significant increase in the rate of embryos reaching the four-cell stage (16.0 vs. 26.7%, P < 0.01), the eight-cell stage (12.1 vs. 25.8 or 23.5%, P < 0.01), and blastulation (8.9 vs. 23.5 or 17.5%, P < 0.01) was observed when the embryos were cultured in a medium containing 10(-8) or 10(-6) M melatonin. These results demonstrate that melatonin supports fertilization and early embryo development after in vitro fertilization.

Plasma catecholamine responses during laparoscopic gynecologic surgery with CO(2) insufflation.

STUDY OBJECTIVE: To compare adrenergic-sympathetic responses during pelvic laparoscopic surgery with CO(2) insufflation with those during laparotomy. DESIGN. Prospective study (Canadian Task Force classification II-1). SETTING: Tertiary care university hospital. PATIENTS: Twenty-one infertile women with a clinical diagnosis of endometriosis. INTERVENTION: Plasma norepinephrine (NE) and epinephrine (E) levels were measured in patients undergoing laparoscopic or open pelvic surgery. MEASUREMENTS AND MAIN RESULTS: During laparoscopic surgery, increases in NE and E levels were correlated with arterial tension of CO(2) (PaCO(2)) and were greater in patients with a larger increase in PaCO(2) than in those undergoing laparotomy. Hemodynamic changes were also more evident during laparoscopic surgery, with larger PaCO(2) increases. CONCLUSION: The PaCO(2) increases due to CO(2) insufflation are associated with adrenergic-sympathetic activation and hemodynamic changes during laparoscopic pelvic surgery.

Eficacia clínica de fosfomicina trometamol 3g (monurol) en el tratamiento de la cistitis aguda / Clinical efficacy of fosfomycin trometamol 3g (monurol) in the treatment of acute cystitis

Objetivo del estudio: Comprobar la eficacia y buena tolerancia de fosfomicina trometamol 3g en dosis única en el tratamiento de la cistitis aguda. Diseño del estudio: Estudio clínico multicéntrico. Selección de pacientes: Mujeres entre 18 y 75 años que acudieron a la consulta ambulatoria con un cuadro clínico de cistitis aguda con test positivo determinado por la tira reactiva BM-test-LN sin antibioticoterapia previa. Con un máximo de 4 episodios de cistitis en el último año. Método: luego de aceptar voluntariamente participar en el estudio, cada paciente recibió un sobre de fosfomicina trometamol 3g como dosis única, citándolas 7 días después para evaluar la eficacia y tolerancia del fármaco, clínica y objetivamente por las tiras reactivas. Resultados: 90 médicos evaluaron 450 pacientes de su consulta ambulatoria. Predominó el grupo de 18 a 30 años (32.88 por ciento), 45 pacientes (10 por ciento) eran gestantes estando la mayoría (48.89 por ciento) en el primer trimestre del embarazo. El 15.55 por ciento padecían de otra enfermedad, siendo la HTA y diabetes las más frecuentes. La mayoría (61.55 por ciento) acudió por un cuadro recidivante, teniendo como principal molestia disuria (96 por ciento) y polaquiuria (91.77 por ciento). Todas las pacientes tenían nitritos en orina con más de 10-25 leucocitos según evaluación de la tira reactiva. Luego del tratamiento, 81.11 por ciento refirieron que desapareció la sintomatología entre el segundo y tercer día, en el 7.78 por ciento persistió el cuadro clínico. El 90.44 por ciento (407 pacientes) estuvieron asintomáticas y sin nitritos en orina, considerándose clínicamente curados; 31 pacientes (7 por ciento) tuvieron mejoría clínica y en 12 (2.66 por ciento) persistió el cuadro. En relación a la tolerancia, 45 pacientes (10 por ciento) refirieron molestias gastrointestinales leves y moderadas, que cedieron espontáneamente. Conclusión: fosfomicina trometamol 3g (monurol) en dósis única, demostró tener una buena eficacia clínica y tolerancia en el tratamiento de la cistitis aguda. Con desaparición de la sintomatología desde el 2do. día post-tratamiento, siendo de utilidad en embarazo independientemente de la edad gestacional.

Prenatal confirmation of the translocation between chromosome 15 and Y-chromosome by fluorescence in situ hybridization.

A 30-year-old woman and her husband visited our hospital with habitual abortion as the complaint. Chromosome examination revealed a normal 46, XX for her and 46, XY, 15, der (15) t (Y; 15) (q12; p12) for him. After her pregnancy amniocentesis was performed. The karyotype was 46, XX, 15, der (15) t (Y; 15) (q12; p12) pat. ish der (15) (DYZ1+). A female baby was delivered. The growth of the baby was normal at 12 months of age.

Anti-nuclear antibodies in patients with premature ovarian failure.

We examined the prevalence of anti-nuclear antibodies (ANA) in 32 consecutive patients with premature ovarian failure with and without chromosomal abnormalities. Blood samples were taken for karyotype determination as well as detection of autoantibodies, X-terminal microdeletions and spontaneous follicular growth. The correlation between ANA positivity and the age at onset of amenorrhoea, as well as the presence of karyotype abnormalities, X-terminal microdeletions and follicular growth was determined. Ten of the 24 patients with normal karyotype and none of the 8 patients with karyotype abnormalities were ANA positive. ANA were found more frequently in patients with premature ovarian failure with normal karyotypes than in control amenorrhoeic patients (42 versus 6, P < 0.01). ANA were found in 77% (10/13) of premature ovarian failure patients with normal karyotypes who developed amenorrhoea at or under the age of 30 years, but not in the patients who developed amenorrhoea later in life. Follicular growth was evident in 50% (5/10) of karyotypically normal patients with ANA, 71% (10/14) of karyotypically normal patients without ANA and 38% (3/8) of patients with karyotype abnormalities. X-terminal microdeletions were not found in any of the patients studied. These results suggest that patients with premature ovarian failure and ANA are an aetiologically and clinically distinct group.

Melatonin, its precursors, and synthesizing enzyme activities in the human ovary.

The presence of melatonin (N-acetyl-5-methoxytryptamine) and its precursors, serotonin (5-hydroxytryptamine) and N-acetylserotonin, was demonstrated in extracts of human ovary using reverse-phase high-performance liquid chromatography coupled with fluorometric detection. In addition, activities of two melatonin-synthesizing enzymes, arylalkylamine N-acetyltransferase (NAT) and hydroxyindole-O-methyltransferase (HIOMT), were found in human ovary homogenates. The apparent Michaelis constants for the substrates of NAT and HIOMT in the human ovary were similar to those reported for the pineal glands of humans and other mammals. These findings strongly suggest that the human ovary, like the pineal gland, may synthesize melatonin from serotonin by the sequential action of NAT and HIOMT.

[Role of irradiation in breast conservation therapy for breast cancer].

Despite a worldwide consensus on the indication for breast conservation therapy (BCT), the proportion of patients treated with BCT in Japan was only 29.2% in 1997. Indications of BCT and opinions against increasing the number of BCT in Japan are discussed along with the concept of evidence-based medicine (EBM). It is evident that in Japan as well, 70% to 90% of patients with breast cancer can be treated with BCT. The main aim of irradiation in BCT is to reduce inbreast recurrences (IBR), and randomized controlled trials have confirmed that irradiation to the breast reduces IBR. Currently, much concern is being directed to the issue of surgical margins in partial mastectomy, i.e., the definition of positivity of margins and how to treat margin-positive cases. The role of boost irradiation to the tumor bed and irradiation to lymph node areas are also discussed.

Immunohistochemical analysis of a case of gastritis cystica profunda associated with carcinoma development.

We report a rare case of gastritis cystica profunda (GCP) accompanied by carcinoma that developed in a 51-year-old Japanese man without antecedent gastric surgery. The polypoid tumor was located in the upper body of the resected stomach. Histologically, it was characterized by herniation of surface epithelium and cystic glands in the submucosa, muscularis propria, and subserosa. Marked chronic atrophic gastritis was found throughout the stomach, and dysplastic epithelia and a few adenocarcinoma cells were found in the deeper parts of the GCP. The Ki-67, p53, and p21WAF1/CIP1 labeling indices for the deeper part of the GCP were higher than those for the superficial parts or the surrounding mucosa, suggesting that both epithelial cell proliferation and p53-dependent p21WAF1/CIP1 expression in DNA-damaged cells, which might be associated with gastritis, are enhanced in line with penetration of glands. The underlying mechanisms might be linked in a chain of factors leading to malignancy.

Coexpression of cholesterol sulfate and cytokeratin as tumor markers in well-differentiated squamous cell carcinoma of the human uterine cervix.

The expression of cholesterol sulfate (CS) is known to increase during squamous differentiation of keratinocytes and to activate the epsilon, eta, and zeta forms of protein kinase C as a signal transduction molecule for the subsequent expression of transglutaminase-1 (TG-1) and cytokeratins. To gain further insight into the regulation of cellular differentiation and tumorigenesis by CS, we examined the concentration and the potential for synthesis of CS in seven and four surgical specimens from human ovarian and uterine cervical cancer patients, respectively, and eight cell lines established from human uterine cervical cancer patients and compared them for the rate of expression of cytokeratin. CS was present in all of the uterine cervical cancer tissue specimens but only in the mucinous type of cystadenocarcinoma among ovarian cancer tissue specimens, and cytokeratin was highly expressed in the tissues with a high concentration of CS, which were classified as well-differentiated on the basis of morphological examination. Similarly, cells derived from a keratinizing type of well-differentiated cervical carcinoma demonstrated strong potential for synthesis of CS, stained positive with anti-cytokeratin antibody, and exhibited a higher specific activity of TG-1, whereas the cells without CS did not stain positive with anti-cytokeratin antibody and exhibited a lower specific activity of TG-1. These findings indicate that CS is coexpressed with TG-1 and cytokeratin in the well-differentiated types of squamous cell cancers as a tumor marker.

Selection of human ovarian carcinoma cells with high dissemination potential by repeated passage of the cells in vivo into nude mice, and involvement of Le(x)-determinant in the dissemination potential.

Cells of the human tumor cell line RMG-1, derived from a clear-cell adenocarcinoma of the ovary, were injected intraperitoneally into nude mice, and the cells obtained from the tumor nodules in the mesenterium were found to form a larger number of, and larger-sized, tumor nodules than the original RMG-1 cells. The RMG-1-h cells, transferred into culture from the tumor nodules after a 4th in vivo passage, showed a dissemination potential as high as that of cells disseminating directly from the tissues, and exceedingly higher than that of RMG-1 cells. To assess the molecular bases of the different biological properties of RMG-1 and RMG-1-h cells, we compared the content and expression of various carbohydrate antigens in both cells. The chromosomal profile of RMG-1-h cells revealed their human origin and was identical to that of the original RMG-1 cells. In contrast to the broad histogram for the Le(x)-bearing cells among RMG-1 cells in flow cytometry, the weakly and moderately positive cells toward anti-Le(x) antibody were found to be eliminated from the histogram for the RMG-1-h cells, resulting in the enrichment of cells strongly expressing Le(x), which may account for the high dissemination potential. In addition, the adhesion of RMG-1 cells to mesothelial cells was found to be significantly inhibited by pretreatment of the cells with anti-Le(x) antibody, indicating Le(x)-mediated cell-to-cell interaction between ovarian cancer cells and mesothelial cells. By TLC-immunostaining, two Le(x)-glycolipids, III3Fuc alpha-nLc4Cer and V3Fuc alpha-nLc6Cer were detected in both RMG-1 and RMG-1-h cells, and their total concentrations were not significantly different from each other. However, the hydrophobic moieties of Le(x)-glycolipids in RMG-1-h cells were different from those in RMG-1 cells, suggesting that a difference in the structure of the hydrophobic moieties of Le(x) is partly involved in the enhanced reactivity of RMG-1-h cells toward anti-Le(x) antibody. Thus, the high dissemination potential of ovarian cancer cells was shown to be mediated by the Le(x)-determinant and the Le(x)-bearing cells are enriched by repeated in vivo passage of the cells into nude mice.

Nitric oxide gas infusion to the oxygenator enhances the biocompatibility of heparin coated extracorporeal bypass circuits.

Heparin coated bypass circuits have been reported to improve the biocompatibility of extracorporeal circulation, although it is still insufficient and improvable. Nitric oxide (NO) is known to inhibit platelet activation and inflammatory reactions. In this study, the authors evaluated exogenous NO infusion in enhancing the effect of a heparin coated bypass circuit on the biocompatibility of an extracorporeal circuit, especially in view of the attenuation of the inflammatory response. A miniature closed bypass circuit, including an oxygenator (BioActive surface; Carmeda, Stockholm, Sweden) was primed with fresh human heparinized blood and perfused with a centrifugal pump. Either pure N2 gas (control group: n = 7) or NO gas (NO group [100 ppm in N2]: n = 7) was infused to the oxygenator. NO metabolites (nitrite and nitrate), platelet count, thrombin-antithrombin III complex (TAT), alpha2-plasmin-plasminogen inhibitor complex (PIC), beta-thromboglobulin (beta-TG), platelet factor 4 (PF4), serotonin, complement 3 activation products (C3a), granulocyte elastase, and bradykinin were measured at 0, 30, 60, 120, and 180 min after starting perfusion. At every sampling point, platelet counts were significantly higher, and TAT, beta-TG, and bradykinin were lower in the NO group than in the control group. PF4, C3a, and granulocyte elastase were significantly lower in the NO group at 60, 120, and 180 min. These results suggest that NO gas infusion to the oxygenator enhances the biocompatibility of heparin coated extracorporeal circuits.