Prediction of ovarian reserve based on day-3 serum follicle stimulating hormone concentrations during the pituitary suppression cycle using a gonadotropin releasing hormone agonist in patients undergoing in vitro fertilization-embryo transfer.

Satisfactory results following in vitro fertilization-embryo transfer (IVF-ET) treatments depend on retrieving an appropriate number of mature oocytes without causing the development of ovarian hyperstimulation syndrome (OHSS). The present study was carried out to investigate whether the ovarian reserve is predictable based on the day-3 serum concentration of follicle stimulating hormone (FSH) during the pituitary suppression cycle using a gonadotropin releasing hormone (GnRH) agonist (defined as day-3 FSH) in patients undergoing IVF-ET treatment. Day-3 FSH before the administration of gonadotropin was assessed in 72 IVF-ET cycles from 59 infertile women. The mean+/-SD of day-3 FSH, the total amount of FSH plus human menopausal gonadotropin (hMG) administered, and the total number of oocytes retrieved was 5.5+/-2.6 mIU/ml, 2834.2+/-1236.5 IU and 7.7+/-5.8, respectively. There were significant correlations between day-3 FSH and the total amount of FSH-hMG administered (p < 0.001), and day-3 FSH and total number of oocytes retrieved (p < 0.001). There was a significant difference of day-3 FSH between patients who subsequently conceived (4.4+/-1.3 mIU/ml) and those who did not conceive (6.1+/-2.9 mIU/ml) (p = 0.001). There was also a significant difference of day-3 FSH between patients who developed moderate or severe OHSS (4.5+/-1.2 mIU/ml) and those who did not (5.9+/-2.8 mIU/ml) (p = 0.003). Receiver-operator characteristic curve analysis showed that the significant cut-off point for day-3 FSH for predicting ovarian reserve was 5.25 mIU/ml. These findings indicate that day 3-FSH is usefulfor predicting ovarian reserve during the pituitary suppression cycle using a GnRH agonist in patients undergoing IVF-ET.

Treatment for ovarian hyperstimulation syndrome using an oral dopamine prodrug, docarpamine.

Dopamine treatment constitutes a major advance towards the management of severe ovarian hyperstimulation syndrome (OHSS) by causing renal and mesenteric vasodilatation as well as diuretic and positive inotropic actions. Docarpamine, an oral dopamine prodrug, is converted into dopamine after enteral administration, and the generated dopamine causes renal vasodilatation and diuresis. The purpose of this study was to assess whether docarpamine had beneficial effects in patients with OHSS. Twenty-seven patients, hospitalized because of OHSS and refractory to the initial therapy with intravenous albumin, were treated by docarpamine, after informed consent had been obtained. A 750-mg tablet of docarpamine was taken every 8 h. In some cases, the plasma levels of free dopamine were measured. The daily urinary outputs before and 1, 2, 3 and 4 days after the docarpamine treatment were 839 +/- 424 ml, 1121 +/- 608 ml, 1168 +/- 504 ml, 1325 +/- 815 ml and 1133 +/- 509 ml, respectively. There were significant differences between the first and each of the others (p < 0.05). In 19 (86.4%) of 22 patients treated, clinical symptoms associated with ascites were gradually improved after administrating docarpamine. The plasma free dopamine concentration rose to as high as 55.9 +/- 33.2 mg/ml during the first hour, which corresponded to the usual intravenous drip infusion treatment with dopamine. Moreover, there were no major adverse effects of docarpamine in this study. This was the first demonstration of docarpamine treatment in patients with intravenous albumin-resistant OHSS. Although no effect was seen in pregnant women, diuresis was increased in some women, and ascites decreased. These findings indicate that oral docarpamine administration could be one of the options in the management of patients with OHSS using dopamine therapy.

The inhibitor of apoptosis protein survivin is associated with high-risk behavior of neuroblastoma.

BACKGROUND/PURPOSE: Apoptotic factors inducing or preventing cell death may intrinsically govern the behavior of some tumors. Survivin is a recently described member of the inhibitor of apoptosis protein (IAP) family, that is expressed in a cell cycle-dependent manner and is found in tumors of unfavorable histology. This study examines the presence of several apoptotic factors, including survivin, in neuroblastoma (NB) tumors. Clues to survivin's function in NB are provided by examining its association with behavior and cell dynamics in tumors and cell lines. METHODS: Expression of a panel of apoptosis factors were quantified in 15 NB and related tumors before chemotherapy and in 3 NB cell lines (NB7, NB10, and NB16). Survivin and other apoptotic factors, as well N-myc amplification in primary tumors was correlated with recurrent disease and outcome. Proliferation rate, apoptosis assays, cell cycle analysis, and drug- or immune-mediated cell death were assessed in cell lines and evaluated in the context of differential survivin and apoptosis gene expression. RESULTS: All 7 tumors that went on to recur expressed survivin, whereas expression was absent in all 8 tumors that went into remission. N-myc was amplified in 4 (57.1%) of the 7 recurrent tumors. Of the 8 tumors that were cured, Fas was expressed in 3 (38%), TRAIL-R1 in 6 (75%) and tumor necrosis factor (TNF)-R1 in 8 (100%), whereas these pro-apoptotic receptors were present in only 1 (14%), 1 (14%), and 4 (57%) of the 7 tumors that went on to recur, respectively. Of the 3 cell lines, NB10 expressed the least survivin, displayed the lowest proliferation index, and had the fewest number of cells in the G2/M (mitotic) phase of the cell cycle. Furthermore, NB10 also was most sensitive to TNF-related apoptosis-inducing ligand (TRAIL) or etoposide-induced cell death. CONCLUSIONS: In primary NB tumors, survivin expression was associated with tumors of high risk and unfavorable prognosis, whereas pro-apoptotic receptor expression was more abundant in tumors of favorable prognosis. In this small series, survivin expression appeared to be more predictive of recurrent disease than N-myc amplification. In cell lines, survivin expression was cell cycle dependent, and its expression was associated with greater proliferation rates and greater resistance to drug- or immune-mediated cell death. Survivin expression may become a useful prognostic marker in NB and could be a potential target for the treatment of this tumor. J Pediatr Surg 36:1785-1791.

Usefulness of transvaginal hydrolaparoscopy in investigating infertile women with Chlamydia trachomatis infection.

BACKGROUND: A new technique called transvaginal hydrolaparoscopy (THL) was recently developed for the exploration of the tubo-ovarian structures in infertile patients without obvious pelvic pathology. This study was performed to investigate the usefulness of THL to evaluate Chlamydia trachomatis tubal infertility. METHODS: Forty-one women with primary and secondary infertility participated in this study. Fourteen had past C. trachomatis infection. In 38 (92.7%) of the 41, access to the pouch of Douglas was obtained. In total, 71 (93.4%) out of 76 adnexa were clearly visualized. Thirty-seven patients were analysed and compared their tubal passages and peritubal adhesions using both hysterosalpingography (HSG) and THL. Twenty-four tubes from 14 patients with past C. trachomatis infection and 44 tubes from 23 patients without a history of C. trachomatis infection were compared. RESULTS: For the diagnosis of the tubal passage, there were no significant differences in the discrepancy rates between HSG and THL, in patients with and without past C. trachomatis infection. In 14 (58.3%) of the 24 tubes from patients with past C. trachomatis infection and in eight (18.2%) of the 44 tubes from patients without infection, peritubal adhesion was diagnosed only by THL. There was a significant difference in the discrepancy rates of the diagnosis of peritubal adhesion between HSG and THL in the two groups (P = 0.0007 ). CONCLUSIONS: These results suggest that C. trachomatis infection is highly associated with peritubal adhesion which is difficult to diagnose by HSG. Therefore, in C. trachomatis antibody-positive patients, exclusion of tubal pathology by THL or standard laparoscopy should be carried out to consider appropriate treatments. Although THL is not a substitute for laparoscopy, it can be proposed as a first line procedure in the early stages of the infertility investigation.

Relationships between sperm motility characteristics assessed by the computer-aided sperm analysis (CASA) and fertilization rates in vitro.

PURPOSE: Some studies have suggested that computer-aided sperm analysis (CASA) estimates of concentration and movement characteristics of progressively motile spermatozoa are related to fertilization rates in vitro. However, it has also been suggested that the greater number of motility parameters assessed by CASA does not imply more precision in predicting fertility. This study was carried out to investigate the relationships between the CASA estimates and fertilization rates in vitro. METHODS: Semen quality analysis was performed using CASA in 136 in vitro fertilization-embryo transfer (IVF-ET) cycles with at least 3 oocytes collected. The CASA estimates before and after swim-up were compared between 108 cycles with fertilization rate > 50% ("good" group) and 28 cycles with fertilization rate < or = 50% ("poor" group). RESULTS: Before swim-up, there were significant correlations between fertilization rates and CASA estimates, including amplitude of lateral head displacement (ALH) (r = .269), curvilinear velocity (VCL) (r = .297), straight line velocity (VSL) (r = .266), and rapid sprm movement (Rapid) (r = .243). There was also a significant correlation between the fertilization rates and straightness (STR) after swim-up (r = -0.178). As for sperm movement characteristics, there were significant differences of ALH (p < .005), VCL (p < .001), VSL (p < .005), and Rapid (p < .01) between "good" and "poor" groups before swim-up. After swim-up, there were significant differences of VCL (p < .005), average path velocity (VAP) (p < .005), and Rapid (p < .05) between the two groups. CONCLUSIONS: These results indicate that some of the CASA estimates provide reliable estimation of the fertilizing ability of human sperm. There were significant differences of the two sperm movement characteristics, including VCL and Rapid (before and after swim-up), indicating that the total distance traveled by rapid sperm movement might be important in human sperm fertilizing abilities.

Erythropoietin synthesis by tumour tissues in a patient with uterine myoma and erythrocytosis.

We report a patient with uterine myoma (leiomyoma) and erythrocytosis in whom erythropoietin (Epo) production in the leiomyoma tissue was identified by reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). A 48-year-old Japanese woman with uterine myoma showed marked erythrocytosis (haemoglobin: 20.2 g/dl, haematocrit: 61.1%, red blood cells: 6.51 x 10(12)/1). After hysterectomy, erythrocytosis rapidly disappeared. In the leiomyoma tissue collected from the patient, Epo mRNA expression was confirmed using RT-PCR. Furthermore, ELISA showed that the Epo protein level was significantly increased compared with those in control tissues. It is suggested that the pathogenesis of erythrocytosis in patients with uterine myoma involves ectopic Epo production by leiomyoma tissues.

Prediction of unexpectedly poor fertilization and pregnancy outcome using the strict criteria for sperm morphology before and after sperm separation in IVF-ET.

This study was performed to investigate if unexpectedly poor fertilization and in-vitro fertilization (IVF) outcome could be predicted using sperm morphology as diagnosed by the strict criteria. Sperm morphology was assessed in 137 IVF-ET cycles with at least three oocytes collected. The lowest amount of normal forms was 5% in 137 samples, indicating there were no patients belonging to 'poor prognosis' (<5% normal forms). Treatment using intracytoplasmic sperm injection (ICSI) was also excluded. Before sperm separation by the swim-up method, sperm morphology demonstrated a significant correlation with the fertilization rate (p < 0.0001). The fertilization rate (80.5%) in 110 'normal' samples (>14% normal forms) was significantly higher (p < 0.01) than that (55.4%) in 27 samples with 'good prognosis' (those with 5--14% normal forms). No embryo was available for transfer (ET) in 4 (3.6%) of 110 'normal' cycles and in 3 (11.1%) of 27 'good prognosis' cycles (not significant). Fresh ET was intentionally cancelled to avoid severe ovarian hyperstimulation syndrome (OHSS) in six of 110 'normal' cycles as well as in one of 27 'good prognosis' cycles. The pregnancy rate per ET was 31.0% (31/100) in the former group, while it was 26.1% (6/23) in the latter group. There was no difference between the two groups. In the post swim-up evaluation of sperm characteristics, morphology was significantly correlated with the fertilization rate in IVF-ET (p < 0.05) while other sperm parameters were not. When the cut off level for the post swim-up sperm morphology was set at 25%, there was a significant difference in the fertilization rates between patients (78.6%) with post-swim-up >25% and those (55.0%) with post-swim-up < or =25% (p < 0.01). Taken together, a relative indication for ICSI using sperm morphology before and after swim-up was established. Category A includes < or =14% normal forms in the ejaculate and post-swim-up < or =25%, while Category B includes < or =14% in the ejaculate and post-swim-up >25%. There was a significant difference in the fertilization rates between patients (47.2%) in Category A and those (60.2%) in Category B (p < 0.05). The clinical pregnancy rate was 11.1% for patients in Category A compared with 35.7% for patients in Category B. However, there was no significant difference between the two categories. These results indicate that the strict criteria provide a reliable estimation of the fertilizing ability of human spermatozoa. ICSI might be considered in Category A patients to avoid poor fertilization and pregnancy outcome.

The survivin:fas ratio in pediatric renal tumors.

BACKGROUND/PURPOSE: Apoptosis factors inducing or preventing cell death may govern the behavior of certain tumors. Fas is a pro-apoptotic receptor that induces cell death when bound by its ligand and is expressed at greater levels in pediatric renal tumors of good prognosis. Survivin is a novel inhibitor of apoptosis that is expressed in a cell cycle-dependent manner and is abundantly expressed in several tumors of unfavorable histology. This study evaluates the expression of survivin, as well as the prognostic value of the survivin:fas ratio in various types and stages of pediatric renal tumors. METHODS: Multiple apoptosis mRNA species were quantified by Rnase protection assay (RPA) in 32 pediatric renal tumors and adjacent normal kidney specimens before chemotherapy: Wilms' tumor (WT), n = 9; clear cell sarcoma (CCS), n = 4; rhabdoid tumor of the kidney (RTK), n = 5; mesoblastic nephroma (MN), n = 3 and normal kidney, n = 11. Western Blot and immunocytochemistry were used to confirm survivin protein expression in a selective specimen survey. Follow-up data were obtained on patient outcomes, and antiapoptotic to proapoptotic ratios were calculated and correlated with clinical recurrence of disease. RESULTS: Pediatric renal tumors express greater levels of both pro- and antiapoptotic factors than normal kidney. Survivin and fas appeared to be expressed differentially in the tumor specimens sampled. Five of 10 (50%) tumors that went on to recur expressed survivin, whereas survivin was present in only 2 of 11 (18%) nonrecurrent tumors. Conversely, only 2 of 10 (20%) tumors that recurred were fas positive, whereas 5 of 11 (45%) tumors that did not recur expressed fas. The mean survivin:fas ratio was significantly greater in the 10 tumors that went on to recur after treatment (4 RTK, 3 CCS, 3 WT), than in tumors not recurring (2.16+/-1.4 v 1.0+/-1.07; P =.01, Kruskal-Wallis test). The positive predictive value of tumor recurrence was 85.7% (CI: 42.1%, 99.6%) and the negative predictive value was 71.4% (CI: 41.9%, 91.6%) when a cutoff ratio of 1.6 was considered. CONCLUSIONS: The survivin:fas mRNA ratio is of prognostic value in its ability to predict recurrent disease in children undergoing treatment for pediatric renal tumors. In this series, a ratio of greater than 1.6 predicted recurrent disease with a high probability irrespective of clinical stage or pathologic type. Determining the survivin:fas ratio may guide treatment, follow-up and counseling of patients with pediatric renal tumors.

Xanthogranulomatous pyelonephritis in childhood: a rare but important clinical entity.

PURPOSE: Xanthogranulomatous pyelonephritis (XGPN) is extremely rare in children. The authors review their experience of this condition. METHODS: Medical records were investigated to conduct a retrospective study of 4 patients with XGPN (3 boys, 1 girl; age range, 2 months to 7 years) at the authors' institute over the past 14 years. RESULTS: Three of the 4 patients presented with fever of unknown origin and 1 with general fatigue. An abdominal mass was palpable in two cases at initial presentation. Although all patients had pyuria or hematuria, preoperative urine culture was positive in only 2 cases. Preoperative radiologic studies showed that 1 kidney was affected completely in 2 cases and affected partially in 2 cases. Preoperatively, the provisional diagnosis was XGPN in 3 cases, and Wilms' tumor in 1 case. Total nephrectomy was performed in 3 cases and enucleation in 1 case. XGPN was confirmed in all cases by histopathologic studies, but the underlying disease could be identified only in 1 case (cystinuria). All patients did well postoperatively and have had no further health problems over a mean follow-up period of 4.8 years. CONCLUSIONS: XGPN should be considered when there is a history of recurrent or therapy-resistant pyelonephritis. Preoperative radiologic investigation is paramount for diagnosis, and nephrectomy is the treatment of choice, although partial resection or enucleation are adequate for partially affected kidneys.

Overexpression of Fas-ligand by neuroblastoma: a novel mechanism of tumor-cell killing.

BACKGROUND/PURPOSE: Binding of Fas ligand (Fas-L) to the membrane-bound Fas receptor incites a series of intracellular events that results in programmed cell death or apoptosis. Although this apoptotic phenomenon plays a key role in down-regulating cytotoxic T cells, the authors have shown previously that pancreatic beta cells (bTC) overexpressing Fas-L paradoxically undergo accelerated rejection that is dependent on a Fas/Fas-L interaction. This study evaluates whether a neuroblastoma (NB) cell line manipulated to overexpress Fas-L undergoes similar destruction and whether tumor-specific protective immunity can be produced. METHODS: The authors transfected NB cells (SK-N-MC) with either mFas-L cloned into a pcDNA3.1/Zeo plasmid vector (NB/Fas-L) or with the vector alone (NB/control). Successful transfection of Fas-L was characterized by reverse transcription polymerase chain reaction (RT-PCR) and the ability of transfectants to induce apoptosis of Fas-sensitive T cells (Jurkat). Expression of Fas and Fas-L in untransfected NB clones was characterized by immunohistochemistry and RNase protection assay (RPA). Apoptosis was measured by FACScan analysis using an Annexin V assay. A total of 3x10(6) NB/control and NB/Fas-L cells were implanted subcutaneously into the hind leg of Balb/C SCID mice. Tumor-specific protective immunity was also tested in this model by inoculating mice with NB/Fas-L before implanting NB/control cells. RESULTS: Zeocin resistance and RT-PCR confirmed successful transfection of Fas-L into NB cells. Fas Ligand transfectants induced apoptosis in 17.6%+/-2.9% of Fas-sensitive T cells, whereas controls induced apoptosis in only 2.8%+/-1.2% (P = .01, n = 3). Although Fas appears to be constitutively expressed by NB in low amounts, introduction of Fas-L into NB cells did not induce suicide or affect tumor cell growth in vitro. In vivo, NB cells expressing Fas-L failed to grow in SCID mice (n = 3), whereas controls grew rapidly in all animals until death (n = 3). NB/control cells implanted into the opposite leg of mice that rejected initial NB/Fas-L transfectants also grew rapidly (n = 3) implying no protective immunity. CONCLUSIONS: Overexpression of Fas-L in NB clones targets such cells for rapid destruction even in immune compromised hosts, suggesting potential utility of Fas-L in combating NB. In this SCID mouse model, the observed effect is probably neutrophil mediated and does not provide tumor-specific protective immunity.

Differential apoptosis gene expression in pediatric tumors of the kidney.

BACKGROUND/PURPOSE: Apoptosis, or programmed cell death, is essential in maintaining normal homeostasis of tissues. The process of apoptosis is controlled by numerous pro- and antiapoptotic factors. Variations in expression of such factors may account for some variations in tumor behavior. This study evaluates the expression of apoptotic mRNA species in pediatric renal tumors to determine whether a pattern of differential apoptosis gene expression correlates with tumor grade and type. METHODS: Twenty-five frozen tissue specimens were obtained from patients undergoing biopsy or resection of pediatric renal tumors before chemotherapy: Wilms' tumor stage II (WT-II, n = 4); Wilms' tumor stage III/IV (WT-III/IV, n = 4); clear cell sarcoma of the kidney stage III (CCSK, n = 2); rhabdoid tumor of the kidney stage III/IV (RTK, n = 4); and normal kidney (NK, n = 11). An RNase Protection Assay (RPA) was performed for 19 pro- and antiapoptotic mRNA species to detect and quantify expression (percentage of GAPDH expressed). Expression of specific mRNAs of interest were confirmed by Western Blot (WB). RESULTS: The expression of apoptotic mRNA species varied markedly between tumors. WT-II expressed greater amounts of proapoptotic receptor mRNA than CCSK or RTK. (Fas, 17.0+/-2.7% v. 2.5+/-0.5% v. 3.3+/-0.9%; P<.02; DR5, 77.0+/-8.8% v. 13.5+/-0.5% v. 27.0+/-4.8; P<.001; TNF-R, 71.3+/-17.0% v. 21.0+/-4.0% v. 29.0+/-5.0%; P<.07, respectively). Surprisingly, antiapoptotic factors (e.g., bcl-2 and bcl-xl) were not overexpressed in poor prognostic tumors (CCSK, RTK) compared with those with good prognosis (WT). Expression of TRAIL (a ligand for DR4 and DR5) was significantly lower in CCSK and RTK than in normal kidney (9.5+/-1.5% v. 56.1+/-10.1%; P = .01). CONCLUSIONS: Proapoptotic receptors are expressed at greater levels in good prognostic tumors, and this finding is compatible with their clinical behavior. Knowledge of differential apoptotic gene expression is of potential value in predicting prognosis and treating such tumors with targeted ligands.

Risk of complications and uterine malignancies in women undergoing hysterectomy for presumed benign leiomyomas.

OBJECTIVES: To determine the incidences of complications and uterine malignancies among women undergoing hysterectomies for presumed benign leiomyomas. METHODS: We retrospectively reviewed the medical records of 923 women who underwent total hysterectomies between January 1983 and December 1997 at our hospital due to presumed benign leiomyomas. RESULTS: The mean age (SD) of the patients was 44. 5 +/- 5.2 years, 105 +/- 35 minutes was required for the procedure, and 405 +/- 312 ml of blood was lost during the procedure. Forty-one (4.4%) women demonstrated complications of intraoperative hemorrhages and required transfused blood. Urinary tract and bowel injuries occurred in 10 (1.1%) and 2 (0.2%) women, respectively. One woman (0.1%) died from pulmonary embolism that occurred on postoperative day 1. One woman (0.1%) required relaparotomy to control intraabdominal hemorrhage. Uterine malignancies were discovered postoperatively in 4 (0.4%) women, including 2 endometrial carcinoma, 1 leiomyosarcoma, and 1 endometrial stromal sarcoma. CONCLUSIONS: The incidences of complications and unrecognized uterine malignancies were similar to the results of previous studies. Of patients undergoing hysterectomy for presumed benign leiomyomas, the risk of major complications was 6.0% (55/923) and the risk of preoperatively undiagnosed uterine malignancies was 0.4%.

Overexpression of Fas ligand does not confer immune privilege to a pancreatic beta tumor cell line (betaTC-3).

BACKGROUND: Fas ligand (Fas-L) is thought to provide immune privilege to specific tissues and tumors by inducing an apoptotic signal of cytotoxic T cells expressing its Fas receptor. Purpose. The purpose of this work was to evaluate whether an immortalized insulin-secreting cell line (betaTC-3) gains immune privilege by inducing overexpression of Fas-L. METHODS: A lipofection technique was used to transfect a betaTC-3 tumor cell line with a plasmid (pcDNA3.1/Zeo) carrying the Fas-L gene and a zeocin resistance gene. Insertion of Fas-L into betaTC was characterized by reverse transcription polymerase chain reaction (RT-PCR) and the ability of transfectants (betaTC-3/Fas-L) to induce apoptosis of Fas-sensitive T cells. Transfectants and control cells were tested for insulin secretion following which 1 x 10(6) insulin-secreting betaTC-3 and betaTC-3/Fas-L cells were subcutaneously implanted into syngeneic, allogeneic, and Fas mutant (lpr) syngeneic mice. Survival of the insulin-secreting cells was then determined by monitoring serum glucose levels in recipients. RESULTS: Successful transfection of vector resistance gene was achieved in the transfected betaTC-3 cells, which was confirmed by zeocin resistance. RT-PCR in resistant Fas-L clones confirmed the transcription of Fas-L, which was absent in controls. Fas-L transfectants induced 20 +/- 4.2% apoptosis of Fas-sensitive T cells, while controls induced 3.47 +/- 2.3% by flow cytometry (P = 0.04, n = 3). Insulin secretion was equivalent in both betaTC-3 and betaTC-3/Fas-L cells. Syngeneic mice implanted with control betaTC-3 cells died within 3 weeks from hypoglycemia due to overgrowth of betaTC-3 tumor. Implanted Fas-L transfected betaTC-3 cells were killed and had no effect on glycemic status except in Fas mutant hosts, where tumors formed in two of three mice. CONCLUSIONS: Despite the ability of transfected betaTC-3 cells to induce apoptosis of T cells in vitro, expression of Fas-L provided no immune privilege to these cells in vivo, but paradoxically induced killing of betaTC-3 cells even in syngeneic hosts.

Vaginal birth after cesarean delivery: results in 310 pregnancies.

OBJECTIVE: To assess and compare the risk associated with a trial of vaginal birth after cesarean section (VBAC) with the risk of an elective repeat cesarean section. METHODS: A retrospective review of the records of 310 consecutive women who, at the Jichi Medical School Hospital in the 6-year period of 1990 through 1995, had previously undergone a primary cesarean section and gave birth to a singleton infant weighing > or = 2,000 g at > or = 36 weeks of gestation in a subsequent pregnancy. RESULTS: Elective cesarean sections were performed on 96 (31%) of 310 women, and VBACs were attempted by 214 women (69%). Vaginal deliveries were successful in 132 (43%) of the 310 pregnancies. No maternal death or perinatal deaths occurred in either group. A uterine rupture occurred in 2 (0.9%) of the 214 women who attempted a VBAC, and 5 women (2.3%) gave birth to neonates with a 1-minute Apgar score < or = 6. None of the 96 women who underwent an elective cesarean section had such complications, although the difference in these complication rates did not reach a significant level. CONCLUSIONS: A trial of a VBAC significantly reduced the rate of cesarean sections. Although the rates of uterine rupture and neonatal asphyxia were slightly higher in women who attempted a VBAC than in women who underwent an elective cesarean section, obstetricians should offer the option of a trial of labor, because more than one-half of the women with a previous cesarean delivery might have successful vaginal deliveries, and the VBAC-related maternal mortality rate does not reportedly differ between women undergoing a trial of labor and women undergoing an elective repeat cesarean section.

Spontaneous perforation of choledochal cyst: a study of 13 cases.

Of the 187 cases of infantile choledochal cyst treated at our hospitals, we encountered 13 with spontaneous perforation. All cases were under 4 years old. Eight cases were found to have biliary peritonitis and 5 had a sealed perforation. The shape of the extrahepatic bile duct was cystic in 8 and fusiform in 5. The cyst wall around the perforation was filmy and bile was found to be oozing through the thinned wall. Nine perforations were single while 4 cases had multiple perforations. Four of 17 perforations occurred in the posterior part of the cyst wall. Only 1 case of perforation was associated with protein plugs in a common channel, while 7 of the 10 cases of choledochal cyst requiring percutaneous biliary drainage due to signs of raised intrabiliary pressure were found to have protein plugs. We consider that spontaneous perforation of a choledochal cyst is not rare in infancy. The etiology of a perforation must be epithelial irritation of the biliary tract due to refluxed pancreatic juice caused by pancreatico-biliary malunion associated with mural immaturity due to infancy, rather than an abnormal rise in ductal pressure or congenital mural weakness at a certain point.

Hepaticoenterostomy after excision of choledochal cyst in children: a 30-year experience with 180 cases.

In the long-term follow-up of patients with choledochal cyst, postoperative ascending cholangitis and/or stone formation in the intrahepatic bile ducts (IHBD) owing to anastomotic stricture present serious problems. To prevent the formation of anastomotic strictures, some surgeons recently have performed hepaticoenterostomy at the hepatic hilum, with a wide stoma, in all patients with choledochal cyst. The authors of the present study review the surgical procedures performed on a total of 180 children with choledochal cyst and discuss the treatment of choice, with special reference to the types of hepaticoenterostomy. The medical records and radiographs of all patients treated for choledochal cyst between January 1964 and December 1993 at the authors' institutions were reviewed. A total of 180 patients (mean age at time of surgery, 4.3 years) had follow-up for a mean of 11.1 years; 174 of them had cyst excision and hepaticoenterostomy, and six had cystoenterostomy. Of the 174 patients who underwent cyst excision, 171 had a conventional hepaticoenterostomy; two had an intrahepatic cystoenterostomy, and one had a hepaticoenterostomy at the hepatic hilum. IHBD stones with or without cholangitis developed postoperatively in four (2.3%) of the 171 patients who had conventional hepaticoenterostomy. The age at time hepaticoenterostomy of these four patients was 12, 7, 16, and 6 years. Postoperative IHBD stone formation and cholangitis were not found in 121 patients under 5 years of age. The authors recommend conventional hepaticoenterostomy as the treatment of choice for children with choledochal cyst. Hepaticoenterostomy at the hepatic hilum is indicated in only selected cases.

Effects of parathyroidectomy on left ventricular mass in patients with hyperparathyroidism.

The effects of parathyroidectomy on left ventricular muscle volume and mechanical performance were evaluated echocardiographically in 24 patients with secondary hyperparathyroidism due to chronic renal failure and in 7 with primary hyperparathyroidism. Intraventricular septum and posterior wall thickness, left ventricular end-diastolic diameters, shortening fraction, ejection fraction, and left ventricular mass index were measured by M mode recording by the parasternal short axis view prior to parathyroidectomy as baseline and repeated 12 months after parathyroidectomy. Serum basal carboxyterminal parathyroid hormone levels in patients with secondary hyperparathyroidism (34.4 +/- 13.7 ng/ml) were significantly higher than in those with primary hyperparathyroidism (3.4 +/- 5.1 ng/ml; p < 0.0001). At 12 months after parathyroidectomy, intraventricular septum and posterior wall thickness, left ventricular end-diastolic diameter and left ventricular mass index were reduced from 11.8 +/- 3.1 mm, 10.9 +/- 1.7 mm, 53.8 +/- 6.3 mm, 200.8 +/- 57.1 g/m2 to 10.0 +/- 2.1 mm (p < 0.05), 9.8 +/- 1.9 mm (p < 0.05), 50.7 +/- 7.2 mm (p < 0.05), 149.6 +/- 38.7 g/m2 (p < 0.0001), in patients with secondary hyperparathyroidism. In patients with primary hyperparathyroidism, all echocardiographic parameters remained in the normal range and did not show any significant changes before or after parathyroidectomy. From this study, parathyroid hormone at extremely high concentrations as seen in secondary hyperparathyroidism appears to be a cardiotoxic substance. Therefore, all patients with secondary hyperthyroidism should be examined by echocardiography and parathyroidectomy should be considered if myocardial hypertrophy is present.

[Three cases with pelvic dead space infection after total cystectomy caused by methicillin-resistant Staphylococcus aureus (MRSA)--local injection of vancomycin].

We recently had three patients with pelvic dead space infection caused by methicillin-resistant Staphylococcus aureus (MRSA) after total cystectomy for urothelial cancer. All were male and aged from 67 to 74 years old. As for underlying diseases, two of them had bladder cancer and one of them had bladder cancer and right ureteral cancer. Total cystectomy and ileal conduit were performed for two patients with bladder cancer, and total cystectomy, nephroureterectomy and ureterocutaneoustomy were performed for a patient with bladder cancer and ureteral cancer. Pelvic dead space infections caused by MRSA appeared after 15-30 days postoperatively. All patients were cured after we locally administered 0.5 g of vancomycin twice a day for 10-11 days from the drains to the pelvic dead spaces. All patients had preoperative antitumor chemotherapy and the postoperative administrations of beta-lactams in common. From these results, we suggest that local administration of vancomycin is effective for the pelvic dead space infection caused by MRSA after total cystectomy.

[Influence of urine pH and cations on antimicrobial activities of penems].

We compared the antimicrobial activities of penems in human urine with those in Mueller-Hinton broth in order to clarify the usefulness of penems for urinary tract infections. Furthermore, we also investigated the influence of urine components, such as pH, magnesium concentration and calcium concentration, on the antimicrobial activities of penems. Three penems, i.e., imipenem, panipenem and meropenem were employed. And two bacterial strains, i.e., Escherichia coli NIHJ JC-2 and Pseudomonas aeruginosa 18s, were tested. There was no significant difference in MBCs between human urine and Mueller-Hinton broth against E. coli. However, MBCs of penems in human urine was lower than those in Mueller-Hinton broth against P. aeruginosa. On the other hand, MBCs of penems against these two strains were low when urine pH was high or urine calcium concentration was low. No influence of urine magnesium concentration on MBCs of penems was seen. From these results, it was suggested that we should measure the antimicrobial activities of penems not only in Mueller-Hinton broth, but also in human urine, when we administer penems to patients with urinary tract infections. And we should foresee the clinical effects of penems against urinary tract infections paying attention to urine pH of the patients.