Uterine sutures at prior caesarean section and placenta accreta in subsequent pregnancy: a case-control study.

OBJECTIVE: To clarify the effects of uterine myometrial suture techniques at prior caesarean section on the incidence of pathologically diagnosed placenta accreta in placenta praevia with prior caesarean section (PPPC). DESIGN: Case-control study. SETTING: Eleven tertiary referral hospitals in central Japan. POPULATION: A total of 98 cases of placenta praevia, a history of one or more prior caesarean sections, and a history of uterine transverse incision and usage of only absorbable thread for myometrial sutures at the prior caesarean section. Exclusions were a history of myomectomy or Strassmann's operation. METHODS: Cases were grouped into a pathologically diagnosed placenta accreta group (38 cases) and a no accreta group (60 cases). Clinical characteristics including uterine suture methods at prior caesarean section were compared (single-layer versus double-layer closure; continuous versus interrupted sutures in the inner myometrial layer). MAIN OUTCOME MEASURE: The incidence of placenta accreta. RESULTS: No difference was found comparing single-layer with double-layer closure in the incidence of placenta accreta (37.1 versus 39.7%, P = 0.805); however, a significant difference was found comparing continuous with interrupted sutures (58.1 versus 29.9%, P = 0.008). Multivariable logistic regression analysis with stepwise selection for the eight factors meeting the criterion of P < 0.10 in univariate analysis was used, and four independent factors were selected, as follows: gravidity ≥ 3 (adjusted odds ratio, aOR, 3.4, 95% confidence interval, 95% CI, 0.99-11.6, P = 0.050); total praevia (versus non-total, aOR 18.4, 95% CI 3.2-107.0, P = 0.001); anterior/centre placenta (versus posterior, aOR 16.4, 95% CI 3.7-72.2, P < 0.001); and continuous sutures (versus interrupted, aOR 6.0, 95% CI 1.4-25.2, P = 0.015). CONCLUSIONS: In this limited study, a history of continuous sutures on the inner side of the uterine wall showed potential to influence the development of placenta accreta in PPPC patients.

Identification of a functional luciferase gene in the non-luminous diurnal firefly, Lucidina biplagiata.

We isolated a luciferase gene (LbLuc) from the non-luminous diurnal firefly, Lucidina biplagiata, with high similarity to that from the nocturnal firefly, Photinus pyralis. The recombinant LbLuc showed luminescence activity comparable to that of the luciferases from P. pyralis and Luciola cruciata. To understand the non-luminosity of L. biplagiata, we determined the amount of luciferase in the adult specimen using the luciferin-luciferase reaction and found that the content of luciferase in L. biplagiata was estimated to be only 0.1% of that in L. cruciata. As previously reported, the content of luciferin in L. biplagiata was less than 0.1% of that in L. cruciata. Thus, the non-luminosity of L. biplagiata might be explained by low levels of both luciferase and luciferin.

Pregnancy following placental abruption.

The aim of the present study by a retrospective chart review was to examine the recurrence rate after placental abruption. Between 1985 and 1998, 81 patients had a placental abruption. We had 2-year follow-up information about 31 patients and 27 of them had a total of 34 subsequent pregnancies. Recurrent placental abruption was observed in 6 pregnancies in 6 patients (6/27, 22.2%). Of the 6 recurrent placental abruptions, the gestational age was 1-3 weeks earlier than that of previous abruption in 4 patients. One patient delivered a healthy baby after her first abruption and then experienced a second abruption. We conclude that careful management is needed after 30 weeks in pregnant women with a previous history of placental abruption.

Successful pregnancy in a patient having high basal serum levels of sex steroid hormones.

A 25-year-old infertile woman who had higher basal levels of serum progesterone (P) and estradiol (E(2)) was examined. Ultrasonography and gonadotropin-releasing hormone test suggested polycystic ovarian syndrome. The high serum E(2) and P concentration increased even more along follicle growth and after ovulation, respectively. Although the source of the higher levels of steroids was unclear, she became pregnant with artificial insemination of husband's sperm and luteal support with human chorionic gonadotropin administration, and delivered a healthy newborn. Through the present study, we can conclude that the high basal level of P in follicular phase may not always impair reproduction, although several reports stress that it adversely affects oocyte maturation and fertilization, and is harmful to endometrial receptivity.

A survey of vaginal hysterectomy ending in laparotomy.

We did a retrospective study of 1,736 vaginal hysterectomies at Handa City Hospital from 1990 to 1999 with special reference to those 24 cases ending in laparotomy. The duration of operation, estimated blood loss, and uterine (with adnexal) weight of the failed vaginal hysterectomies were 139.1+/-42.9 min, 1,176.8+/-699.8 mL, 564.5+/-357.6 g, respectively. These values were significantly higher than those for the successful vaginal hysterectomies. Adhesions were seen in 14 cases (58.3%). Blood transfusion was required in 9 cases (37.5%). The most frequent cause for laparotomy was adhesions, followed by non-descent of the uterus. The decision to convert a vaginal hysterectomy into an abdominal procedure should be prompt because delay means the increased blood loss and a greater need for blood transfusions.

Fenofibrate improves insulin sensitivity in connection with intramuscular lipid content, muscle fatty acid-binding protein, and beta-oxidation in skeletal muscle.

We investigated the effect of fenofibrate, a peroxisome proliferator-activated receptor-alpha agonist, on insulin sensitivity including lipid metabolism in skeletal muscle. Six-week-old male Sprague-Dawley rats were divided into two groups: those fed a standard chow (control) or a fructose-rich chow (fructose-fed rats (FFRs)) for 6 weeks. FFRs were treated either with a vehicle or with 30 mg/kg per day of fenofibrate for the last 2 weeks. Insulin sensitivity (M-value) was estimated by the euglycemic hyperinsulinemic glucose clamp method. Fatty acid-binding protein (FABP) in skeletal muscle was measured by ELISA, and the expression of FABP mRNA was analyzed by semi-quantitative RT-PCR. The serum and muscle triglyceride (sTG and mTG) levels and the activity of 3-hydroxyacyl-CoA dehydrogenase (HADH), a beta-oxidation enzyme, in muscle were also determined. FFRs showed a lower M-value and higher blood pressure, sTG and mTG than did the control group. The mTG was correlated positively with sTG and negatively with the M-value. Fenofibrate treatment for 2 weeks did not change blood pressure but significantly improved the M-value, sTG and mTG. FABP content and mRNA in the soleus muscle were significantly elevated in FFRs compared with those in the control group. Fenofibrate treatment further increased FABP. The HADH activity was comparable between the control group and FFRs, but significantly increased by fenofibrate treatment. These results suggest that fenofibrate improves insulin sensitivity not only by lowering serum lipids and subsequent influx of fatty acids into muscles but also by reducing intramuscular lipid content via further induction of FABP and stimulation of beta-oxidation in muscles.

Normal nephrogenesis occurs in the early stage of bilateral multicystic dysplastic kidneys.

We present a case report about bilateral multicystic dysplastic kidneys (MCDKs). Pregnancy was terminated at 21 weeks' gestation and the fetus was examined by autopsy. The kidneys were replaced by many cysts and there was no parenchyma. However, on histological examination, there was normal nephrogenesis amid the cystic/dysplastic tissue. This suggests that normal nephrogenesis occurs before the secondary changes leading to MCDKs.

Psoas abscess with osteomyelitis in a patient undergoing long-term hemodialysis.

We describe a 69-year-old male patient on maintenance hemodialysis for 24 years who developed a fatal left psoas abscess with osteomyelitis at the hip joint following acute enterocolitis. He had systemic beta(2)-microglobulin amyloid deposition in colon epithelium and psoas muscle. Cultures from abscess fluid and femoral bone marrow yielded Bacteroides fragilis. To our knowledge, this is the first case on hemodialysis having a psoas abscess following acute gastrointestinal infection. This rare case suggested that a secondary psoas abscess could be one of the occult infections in patients undergoing long-term maintenance hemodialysis.

High blood soluble receptor p80 for tumour necrosis factor-alpha is associated with erythropoietin resistance in haemodialysis patients.

BACKGROUND: Inflammation is one of the major causes of resistance to erythropoietin (rHuEpo) treatment. Tumour necrosis factor-alpha (TNF-alpha), one of the most potent proinflammatory cytokines, is known to inhibit human erythropoiesis directly in vitro. Although blood levels of soluble receptors for TNF-alpha (sTNFRs) are elevated in haemodialysis (HD) patients, the role of sTNFR for rHuEpo responsiveness in HD patients remains to be clarified. METHODS: We measured serum sTNFR (p55 and p80) levels in 83 stable outpatients undergoing regular HD (age 62+/-1, HD duration 15+/-1 years). After dividing the patients into three groups according to rHuEpo dose: (low (L) <60, n=31; moderate (M) > or =60 to <120, n=31; high (H) > or =120 U/kg/week rHuEpo, n=21), we examined the relationship between serum sTNFR levels and the degree of renal anaemia and rHuEpo dosage. RESULTS: Haemoglobin was significantly higher in patients receiving low rHuEpo dosage (L, 10.5+/-0.2; M, 9.7+/-0.1; H, 9.5+/-0.2 g/dl, P<0.01 vs M and H groups). There were no differences in blood TNF-alpha, sTNFR p55, C-reactive protein, albumin, ferritin, or intact parathyroid hormone levels among the three groups. Body mass index and creatinine generation rate, a marker of whole-body muscle volume, were significantly reduced in group H (P<0.01). Serum sTNFR p80 levels were significantly higher in group H (4.88+/-0.45 ng/ml) than in L (3.73+/-0.14 ng/ml) and M (3.67+/-0.21 ng/ml) groups (P<0.05). The blood interleukin (IL)-6 level was also increased in patients requiring high rHuEpo doses (L, 5.5+/-0.5; M, 6.4+/-0.5; H, 10.2+/-2.0 pg/ml, P<0.05 vs L and H groups). A stepwise regression analysis revealed that gender and sTNFR p80 were significant predictors of rHuEpo dosage. A significant direct relationship was found between rHuEpo dose and sTNFR p80 (r=0.499) and IL-6 (r=0.439) values in women (P<0.01) but not in men. CONCLUSIONS: These findings suggest that high blood sTNFR p80 may contribute to the development of rHuEpo resistance in female patients undergoing long-term HD.

Elevation of blood (1-->3)-beta-D-glucan concentrations in hemodialysis patients.

Determination of the blood (1-->3)-beta-D-glucan (beta-DG) concentration is a sensitive marker to detect the presence of deep mycosis and fungal infections. Although cellulose material is known to contain beta-DG, the influence of a cellulose dialyzer membrane on the blood beta-DG level remains to be elucidated. In this study, we determined the plasma beta-DG levels in dialysis outpatients using either a modified regenerated cellulose (MRC) or a synthetic polysulfone (PS) membrane for more than 3 months. Plasma beta-DG levels were extremely high in patients using the MRC (2,778 +/- 549 pg/ml, n = 9) but not the PS membrane (18.8 +/- 3.7 pg/ml, n = 8) compared to normal ranges (<20 pg/ml). A single dialysis session using the MRC membrane further increased blood beta-DG values to 5,561 +/- 722 pg/ml (p < 0.01). After changing the membranes from MRC to PS, the blood beta-DG levels gradually decreased and reached 29.6 +/- 6.0 pg/ml at 6 months. In contrast, the PS membrane did not affect plasma beta-DG levels after a single dialysis session (16.0 +/- 3.9 pg/ml) or 4 months later (24.0 +/- 4.9 pg/ml). These findings suggested that a cellulose membrane could influence the measurement of blood beta-DG concentrations in the long-term. Careful assessment is required to diagnose the presence of fungal infection in HD patients using a cellulose membrane.

Prevalence of asymptomatic ST segment elevation in right precordial leads with right bundle branch block (Brugada-type ST shift) among the general Japanese population.

OBJECTIVE: To examine the modality and morbidity of asymptomatic ST segment elevation in leads V1 to V3 with right bundle branch block (Brugada-type ST shift). METHODS: 8612 Japanese subjects (5987 men and 2625 women, mean age 49.2 years) who underwent a health check up in 1997 were investigated. Those with Brugada-type ST shift underwent the following further examinations over a two year period after the initial check up: ECG, echocardiogram, 24 hour Holter monitoring, treadmill exercise testing, signal averaged ECG, and slow kinetic sodium channel blocker loading test (cibenzoline, 1.4 mg/kg). RESULTS: Asymptomatic Brugada-type ST shift was found in 12 of 8612 (0.14%) subjects. Eleven of these 12 subjects were followed up. Follow up ECG exhibited persistent Brugada-type ST shift in seven of 11 (63.6%) subjects. ST shift was transformed from a saddle back to a coved type in three subjects. None of the subjects had morphological abnormalities or abnormal tachyarrhythmias. Positive late potentials were found in seven of 11 (63.6%) subjects. Augmentation of ST shift was shown by both submaximal exercise and drug administration in one of the 11 subjects (9.1%). CONCLUSIONS: Asymptomatic subjects with Brugada-type ST shift were not unusual, at a rate of 0.14% in the general Japanese population. Almost all of the subjects had some abnormalities in non-invasive secondary examinations. Additional and prospective studies are needed to confirm the clinical significance and the prognosis of asymptomatic Brugada-type ST shift.

Axin facilitates Smad3 activation in the transforming growth factor beta signaling pathway.

Axin acts as a negative regulator in Wnt signaling through interaction with various molecules involved in this pathway, including beta-catenin, adenomatous polyposis coli, and glycogen synthase kinase 3beta. We show here that Axin also regulates the effects of Smad3 on the transforming growth factor beta (TGF-beta) signaling pathway. In the absence of activated TGF-beta receptors. Axin physically interacted with Smad3 through its C-terminal region located between the beta-catenin binding site and Dishevelled-homologous domain. An Axin homologue, Axil (also called conductin), also interacted with Smad3. In the absence of ligand stimulation, Axin was colocalized with Smad3 in the cytoplasm in vivo. Upon receptor activation, Smad3 was strongly phosphorylated by TGF-beta type I receptor (TbetaR-I) in the presence of Axin, and dissociated from TbetaR-I and Axin. Moreover, the transcriptional activity of TGF-beta was enhanced by Axin and repressed by an Axin mutant which is able to bind to Smad3. Axin may thus function as an adapter of Smad3, facilitating its activation by TGF-beta receptors for efficient TGF-beta signaling.

Polymethylmethacrylate efficacy in reduction of renal itching in hemodialysis patients: crossover study and role of tumor necrosis factor-alpha.

Pruritus is one of the major unsolved problems for patients receiving regular hemodialysis. In this study, we conducted a 6 month prospective and crossover trial to investigate the effect of polymethylmethacrylate (PMMA) membrane for renal itching. We also examined the role of the tumor necrosis factor (TNF)-alpha system for pruritus in hemodialysis patients. We assessed the degree of skin itching and measured circulating levels of TNF-alpha and soluble TNF receptors (sTNFR-I, sTNFR-II) in 19 patients using hemodialysis, complicated by prolonged severe pruritus for 6 months. Serum sTNFR-I and II levels were significantly elevated in hemodialysis patients compared to normal subjects. Serum sTNFR-II levels were significantly and negatively correlated with serum albumin (r = -0.602, p = 0.007). A significant positive relationship was also found between sTNFR-I and erythropoietin dosage (r = 0.554, p = 0.016). However, no association was found between the degree of pruritus and circulating sTNFR-I and II values. Skin itching scale was significantly decreased from 2.7 +/- 0.2 to 2.1 +/- 0.3 following the use of PMMA membrane for 3 months (p < 0.05). In contrast, there was no change in itching scales during 3 months of conventional therapy (2.2 +/- 0.3 versus 2.2 +/- 0.3, p = NS). PMMA itself did not affect serum TNF-alpha and sTNFR values as well as conventional dialyzer membranes. These findings suggested that the PMMA dialyzer can improve renal itching not mediated through the modification of the TNF-alpha system.

Human chorionic gonadotropin beta-core fragment is directly produced by cancer cells.

The present study was undertaken to investigate whether hCG beta-core fragment (hCGbeta cf) was directly produced by cancer cells. Fifteen cell lines, including four choriocarcinoma and five ovarian cancer cell lines, were tested, and immunoreactivity of hCGbeta cf was present in the culture media of five of the cell lines. It was also present in the culture media of Chinese hamster ovary (CHO) cells transfected with hCGbeta gene. In addition to hCGbeta cf, gel chromatography and Western blot analysis of the culture media showed the presence of an hCGbeta cf immunoreactive material with a molecular weight of approximately 40 kDa. In an in vivo study, hCGbeta cf immunoreactivity was detected in the sera of the mice transplanted with NaUCC-3 choriocarcinoma cells, although the ratios of hCGbeta cf/hCG and hCGbeta cf/free hCGbeta were lower than those in the culture medium. Incubation experiments of purified hCGbeta cf in the serum showed no substantial decrease in its values, ruling out the possibility that formation of a macromolecule with serum components may mask hCGbeta cf immunoreactivity in the serum. Taken together, these results indicate that hCGbeta cf immunoreactive materials are directly produced by cancer cells and hCGbeta cf is not a urinary metabolite of hCG or hCGbeta alone. Also, reduced levels of hCGbeta cf in the serum compared with that of intact hCG or free hCGbeta are likely due to its short half-life.