[Structural change of the corpus callosum fibers in toddlers with autism spectrum disorder: two-year follow-up].

Objective: To conduct a follow-up investigation of structural changes of the corpus callosum fibers of toddlers (2 to 5 years of age) with autism spectrum disorder(ASD) and to explore the associations with clinical symptoms. Method: In this prospective randomized controlled study, ASD children who were diagnosed in the Child Mental Health Research Center, Nanjing Brain Hospital Affiliated to Nanjing Medical University from May 2011 to November 2012 were included in the ASD group, and developmentally delayed children were included in the control group (DD group). Diffusion tensor imaging (DTI) data from the two groups were obtained at two age levels: 2-3 years of age, and 4-5 years of age. Region of interest analysis was applied to assess characteristic values of total area and sub-regions of corpus callosum: the fraction anisotropy (FA), the mean diffusivity (MD), the radial diffusivity (RD) and the axial diffusivity (AD). All children were assessed using the Autism Diagnostic Interview-Revised (ADI-R) and Autism Treatment Evaluation Checklist (ATEC). The characteristic values of total area and sub-regions of corpus callosum of ASD group at two age levels were analyzed by paired sample t test; the characteristic values of total area and sub-regions of corpus callosum of ASD group and DD group were analyzed by independent-sample t test; the correlations between FA values of the total area and sub-regions of corpus callosum and ADI-R or ATEC scores were analyzed by Pearson correlation analysis. Result: Forty cases meeting inclusion criteria were enrolled in ASD group, and 31 eligible cases were enrolled in the control group. Four children in the ASD group were lost to follow-up, and 5 children in the control group were lost to follow-up. Longitudinal comparison between the two age subgroups of ASD patients showed that the FA values of the total corpus callosum increased (0.499 55±0.027 59 vs. 0.505 83±0.086 64, t=4.88, P<0.05), but MD values, RD values and AD values of the total corpus callosum area decreased (0.000 89±0.000 03 vs. 0.000 81±0.000 14, 0.000 61±0.000 04 vs. 0.000 55±0.000 09, 0.001 43±0.000 03 vs. 0.001 38±0.000 03, t=9.31, 7.90, 8.66, P<0.05 for all comparisons). In the area of corpus callosum genu, FA and AD values increased (t=5.59, 8.48, P<0.05 for both comparisons), but MD and RD values decreased (t=12.67, 11.28, P<0.05 for both comparisns). In the area of corpus callosum body, FA and RD values increased(t=5.46, 8.48, P<0.05 for both comparisons), but MD and AD values decreased (t=8.08, 6.22, P<0.05 for both comparisons). In the area of corpus callosum splenium, MD, RD and AD values decreased (t=6.81, 4.44, 5.51, P < 0.05 for all comparisons). Among the participants 2 to 3 years of age, there were no significantly differences in FA values of total area and sub-regions of corpus callosum between ASD group and the DD group (P > 0.05 for all comparisons); as compared with the DD group, ASD group had higher AD values of total area and splenium of corpus callosum (0.001 43±0.000 03 vs. 0.001 40±0.000 04, 0.001 34±0.000 03 vs. 0.001 32±0.000 04, t=1.56, 1.14, P < 0.05 for both comparisons); ASD group had lower AD values but higher RD and MD values of corpus callosum genu (t=0.07, 0.55, 0.07, P < 0.05 for all comparisons); ASD group had lower RD values of corpus callosum body (t=0.07, P < 0.05). Among the participants 4 to 5 years of age, as compared with the DD group, ASD group had higher FA value of total corpus callosum area(0.505 83±0.086 64 vs. 0.483 77±0.099 30, t=8.56, P < 0.05), lower RD value of total corpus callosum(0.000 55±0.000 09 vs. 0.000 56±0.000 12, t=14.44, P < 0.05), lower RD values of corpus callosum body (t=2.20, P < 0.05), higher FA values (t=3.35, P < 0.05) but lower AD values of corpus callosum splenium (t=2.20, P < 0.05). A correlation analysis between FA values of total area and sub-regions of corpus callosum and clinical variables showed that the FA values of total area and splenium of corpus callosum in ASD group at 2 to 3 years of age were negatively correlated with the scores of language skills in ATEC (r=-0.35,-0.36, P < 0.05 for both comparisons). And after two years, FA values of total corpus callosum were positively correlated with the scores of social communication in ATEC (r=0.34, P < 0.05). There was no significant correlation between FA values of sub-regions of corpus callosum and the scores of ATEC (P > 0.05 for all comparisons). There was no significant correlation between FA values of total area and sub-regions of corpus callosum and the scores of ADI-R (P > 0.05 for all comparisons). Conclusion: The fiber structure of corpus callosum was still in the process of maturing during the age of 2 to 5 years; however, compared with DD group, ASD group had more extensive structural abnormalities of the corpus callosum fibers as age increased, and the structural abnormalities had correlation with the core symptoms of ASD. Trial registration Chinese Clinical Trial Registry, ChiCTR-OPC-17011995.

Correlation of fecundability and serum estradiol after danazol treatment in patients with advanced endometriosis.

OBJECTIVE: To examine the relationship between pregnancy incidence and the level of serum E2 during danazol therapy. DESIGN: Danazol was given by 200 mg four times daily for 3 months. Serum E2 level was checked after completing the therapy, but before stopping medication. Patients then were advised to conceive at the appropriate time over a 6-month period. SETTING: Reproductive and Endocrine Laboratory of the Department of Obstetrics and Gynecology, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan. PATIENTS: Infertile women with invasive endometriosis receiving conservative surgery and danazol treatment. INTERVENTIONS: Serum E2 is checked before medication and at the end of danazol therapy, but before stopping medication. MAIN OUTCOME MEASURES: Whether pregnancy is related to the change of serum E2 caused by danazol therapy. RESULTS: There were 24 pregnancies in 38 patients with invasive endometriosis after treatment. Pregnant patients had significantly lower serum E2 levels as compared with the nonpregnant patients. CONCLUSIONS: After conservative surgery for invasive endometriosis associated with infertility, the therapeutic period of danazol treatment could be shortened to 3 months. Because there is significant correlation of fecundability and serum E2 after danazol medication, serum E2 could be a guideline for predicting pregnancy or for prolonging or changing of treatment after danazol therapy.

Spontaneous intrauterine remission of fetal ascites in one identical twin. Report of a case with ultrasound evaluation.

BACKGROUND: Fetal ascites is usually a precursor of, or one of the findings in, hydrops fetalis. The spontaneous intrauterine remission of fetal ascites, especially in twin pregnancy, is extremely low. CASE: A woman had sonographically documented fetal ascites in one identical twin. The workup for immunologic or nonimmunologic causes was negative except for the absence of end diastolic flow in the umbilical artery, demonstrated by Doppler ultrasonography in the affected fetus. Subsequent sonographic examinations demonstrated disappearance of the ascites as resistance of the umbilical artery progressively improved. CONCLUSION: In evaluating the hemodynamic changes in this condition, Doppler ultrasonography can elucidate the pathophysiology of fetal ascites formation in a monochorionic twin and also provide information for guiding management.

Comparison of laparoscopic presacral neurectomy and laparoscopic uterine nerve ablation for primary dysmenorrhea.

OBJECTIVE: To compare laparoscopic presacral neurectomy and laparoscopic uterine nerve ablation for primary dysmenorrhea. STUDY DESIGN: Sixty-eight patients with primary dysmenorrhea and a poor response to medical treatment were randomized into two groups. One group (33 patients) had laparoscopic presacral neurectomy (LPSN) and the other group (35 patients), laparoscopic uterine nerve ablation (LUNA). RESULTS: There were no complications, and all the patients left the hospital within 24 hours after surgery. The efficacy of both surgical methods was almost equal (87.9% vs. 82.9%) at the 3-month postoperative follow-up visit, but the efficacy of LPSN was significantly better than that of LUNA (81.8% vs 51.4%) at the 12-month visit. CONCLUSION: LPSN is a valid option for treating primary dysmenorrhea.

Interphase fluorescence in situ hybridization in a Turner syndrome variant with IsoXq. A case report.

BACKGROUND: Performing fluorescence in situ hybridization (FISH) on uncultured amniotic fluid cells has been known to produce rapid diagnoses of major chromosomal aberrations. However, if the aberration involves a structural chromosomal anomaly, the FISH result may be not only uninformative but misleading. CASE: FISH with alpha-satellite probes of chromosomes X and Y was performed on the uncultured amniocytes of a prenatal amniotic fluid specimen. Eighty-five percent of the hybridized interphase nuclei displayed two signals when probing with X; no significant hybridization was found when probing with Y. This FISH result was interpreted as normal, disomic for chromosome X. Cytogenetic analysis later, however, disclosed the fetal karyotype to be 46,X,i(Xq). CONCLUSION: Interphase FISH with an alpha-satellite probe (or probe made of repeat centromeric sequences) may be useful in the detection of a numerical anomaly of a chromosome but not of a structural anomaly within the chromosome itself.

Application of Sartwell's model (lognormal distribution of incubation periods) to age at onset and age at death of foals with Rhodococcus equi pneumonia as evidence of perinatal infection.

The distributions of the incubation periods for infectious and neoplastic diseases originating from point-source exposures, and for genetic diseases, follow a lognormal distribution (Sartwell's model). Conversely, incubation periods in propagated outbreaks and diseases with strong environmental components do not follow a lognormal distribution. In this study Sartwell's model was applied to the age at onset and age at death of foals with Rhodococcus equi pneumonia. The age at onset of clinical signs and age at death were compiled for 107 foals that had been diagnosed with R. equi pneumonia at breeding farms in Argentina and Japan. For each outcome (disease and death), these data followed a lognormal distribution. A group of 115 foals with colic from the University of California were used as a comparison group. The age at onset of clinical signs for these foals did not follow a lognormal distribution. These results were consistent with the hypothesis that foals are infected with R. equi during the 1st several days of life, similar to a point-source exposure.

[Operative laparoscopy in gynecology oncology].

Because of the poor sensitivity and accuracy of noninvasive nonsurgical methods of detection of occult pelvic and para-aortic lymph nodes, as well as the cost and discomfort of surgical staging, Keelung Chang Gung Memorial Hospital introduced laparoscopic procedures in the staging of cervical cancer from May 1992. Since then, 112 such surgical procedures have been undertaken, including 36 pelvic lymphadenectomies, 20 para-aortic lymphadenectomies, 6 infrarenal paraaortic lymphadenectomies, 22 simple hysterectomies, 6 extended hysterectomies, 2 Schauta's radical hysterectomies, 4 omentectomies, 5 appendectomies, 3 ovarian transpositions, and 8 second look operations for ovarian cancer. All patients tolerated the procedures smoothly except for one who had hemostasis. There was also one complication of tumor seeding at the laparoscopic skin site. Our preliminary experience shows the feasibility and safety of laparoscopic procedures for gynecology and oncology patients. The potential application of laparoscopy in managing gynecologic malignancies is highly appreciated in our institute. The birth of operative laparoscopy in the subspecialty of gynecologic oncology has taken place.

An infant with rhabdomyoma prenatally diagnosed in a mother with tuberous sclerosis.

We report on an infant with rhabdomyoma diagnosed prenatally by echocardiography which revealed specific patterns of intracardiac tumors. The mother had been previously diagnosed with tuberous sclerosis. Since birth, the infant's intracardiac tumor has regressed and he has shown good growth and development without surgery in more than one year of follow-up. In tuberous sclerosis, a cardiac rhabdomyoma is the only sign that can be detected prenatally by ultrasound. Even though a cardiac rhabdomyoma occasionally induces poor outcome, the need for surgery depends on the patient's clinical presentation.

Subclinical rubella reinfection in pregnancy: report of a case.

A G1 PO, 25-year-old woman, who was confirmed to have a natural immunity to rubella before pregnancy, was found to have rubella reinfection with positive rubella IgM antibody at seven weeks of gestation. At 23 weeks' gestation, she received fetal cordocentesis in which fetal blood tests were negative for rubella-specific IgM. There were also nonspecific findings in detailed sonographic examination. Thereafter, she delivered a healthy, female baby at term. Rubella IgM was not detected in the infant blood at birth and IgG subsided after the first year of life. A primary attack of rubella does not always indicate lifelong immunity; reinfection can occur. Although the symptoms of rubella reinfection are mild and the risk to the fetus from maternal rubella reinfection during pregnancy seems to be lower than that of a primary attack, prenatal evaluation of intrauterine infection by cordocentesis after 23 weeks' gestation should be considered.

Prenatal diagnosis of Dandy-Walker malformation: report of a case.

Dandy-Walker malformation is one of the major causes of congenital hydrocephalus. We report on a case that was diagnosed by sonography in a fetus at 34 weeks' gestation. The diagnosis was confirmed by postnatal computed tomographic (CT) brain scan and magnetic resonance imaging (MRI). The prenatal sonographic findings were a large posterior fossa in communication with the fourth ventricle, a small and splayed cerebellar hemisphere and marked degrees of ventriculomegaly. The postnatal CT scan images were similar to the prenatal sonography. The hypoplasia of the cerebellar vermis and the associated hypogenesis of the corpus callosum can only be clearly delineated by MRI. Dandy-Walker malformation is one form of the Dandy-Walker complex and cystic malformations of the posterior fossa. It should be differentiated from Dandy-Walker variant, or mega-cisterna magna, and arachnoid cyst. Dandy-Walker complex may be associated with chromosomal, intracranial and extracranial abnormalities. Early in utero detection is useful for detailed evaluation of associated anomalies. Obstetric management depends on gestational age, karyotype abnormality and associated intracranial and extracranial anomalies. In the present report, the infant presented no progressive ventriculomegaly and no surgery was required. The infant developed normally.

Laparoscopic management of tubal pregnancy.

Early detection of an unruptured tubal pregnancy has been made possible by the recent use of vaginal sonograms, thus more conservative management can be undertaken. From February 1989 to June 1989, we attempted to treat tubal pregnancies by surgical laparoscopy at the Keelung Chang Gung Memorial Hospital. Fourteen consecutive cases of tubal pregnancy were treated by surgical laparoscopy with a success rate of 70% (10 out of 14). Six of the 10 successfully treated cases were managed conservatively. Use of the laparoscope may be considered as a major trend towards conservative tubal pregnancy treatment, such as salpingotomy for women with an unruptured ectopic pregnancy who want to conserve fertility. These 10 cases of tubal pregnancy benefited enormously from the surgical laparoscopic technique which led to a shorter hospital stay, early ambulation and resume point of normal activities within days. No complications related to surgical laparoscopy were noted in this series. Our conclusion is that surgical laparoscopy should be considered an alternative to laparotomy for the treatment of tubal pregnancy.

Treatment of malignant germ cell tumors of the ovary.

Thirty-five patients with ovarian germ cell malignancies presenting from 1982 to 1992 were studied. The pathologic diagnoses were immature teratoma in 11 patients, endodermal sinus tumor in eight, dysgerminoma in 12, and mixed germ cell tumor in four. The median age at presentation was 20 years. Postoperative multiple-agent chemotherapy was given to 28 patients. Five out of 35 (14%) patients died of malignancy, three with endodermal sinus tumors with stage Ia, Ic, and IIIc, respectively, one with stage IIIc dysgerminoma, and one with stage IIIc mixed germ cell tumor. The other 30 patients were alive without evidence of disease from 14 to 124 months, with a median follow-up of 52 months. All eleven patients with immature teratoma were alive with no evidence of disease at 20 to 104 months of follow-up. Four patients with stage I, grade 1 immature teratoma were successfully treated with surgery alone. The other seven patients were treated with adjuvant chemotherapy and were disease-free. One patient with stage IIIc dysgerminoma was treated with surgery and radiotherapy but died of disease. The other eleven patients were safely treated with surgery and adjuvant chemotherapy with vincristine, actinomycin-D and cyclophosphamide (VAC) or platinum-based chemotherapy. For the more virulent tumors such as endodermal sinus tumor and mixed germ cell tumor, platinum-based chemotherapy should be used exclusively in view of the high failure rate of the VAC regimen. Preservation of fertility for young patients with malignant ovarian germ cell tumors is possible in the early stages of disease and in selected cases of advanced disease.

Estimation of the probability for exceeding a threshold concentration of furosemide at various intervals after intravenous administration in horses.

OBJECTIVE: To estimate the probability for exceeding a threshold concentration of furosemide commonly used for regulatory purposes after IV administration of furosemide in horses. ANIMALS: 12 mature healthy horses (6 Thoroughbreds and 6 Quarter Horses). PROCEDURE: Venous blood was collected from each horse prior to and 0.25, 0.5, 0.75, 1, 2, 3, 4, 4.5, 5, and 6 hours after administration of 250 or 500 mg of furosemide. Concentrations of furosemide were determined, using an ELISA. Concentration of furosemide was modeled as a function of time, accounting for inter- and intrahorse variabilities. On the basis of pharmacokinetic data, the probability for exceeding a concentration of 100 ng/ml as a function of time was determined, using a semiparametric smooth functional averaging method. A bootstrap approach was used to assess inherent variation in this estimated probability. RESULTS: The estimated probability of exceeding the threshold of 100 ng of furosemide/ml ranged from 11.6% at 4 hours to 2.2% at 5.5 hours after IV administration of 250 mg of furosemide/horse and 34.2% at 4 hours to 12.3% at 5.5 hours after IV administration of 500 mg of furosemide/horse. The probability of a horse being falsely identified in violation of regulatory concentrations was inversely associated with time and positively associated with dose. CONCLUSIONS AND CLINICAL RELEVANCE: Interhorse variability with respect to pharmacokinetics of furosemide will result in misclassification of some horses as being in violation of regulatory concentrations.

Estimation of the probability for exceeding thresholds of urine specific gravity and plasma concentration of furosemide at various intervals after intravenous administration of furosemide in horses.

OBJECTIVE: To estimate the probability of concurrently exceeding thresholds for plasma concentration of furosemide and urine specific gravity after IV administration of furosemide in horses. ANIMALS: 12 mature healthy Thoroughbred (n = 6) or Quarter Horse (6) mares. PROCEDURE: Venous blood was collected from each horse prior to and 0.25, 0.5, 0.75, 1, 2, 3, 4, 4.5, 5, and 6 hours after IV administration of 250 mg (first experiment) or 500 mg (second experiment) of furosemide. Urine was collected hourly between 1 and 6 hours after administration of furosemide at both doses. Concentrations of furosemide were determined by use of an ELISA. Concentration of furosemide and urine specific gravity was modeled as a function of time, accounting for inter- and intrahorse variabilities. On the basis of pharmacokinetic and specific gravity data, the probability of exceeding a concentration of 100 ng of furosemide/ml as a function of time was determined, using a semiparametric smooth functional averaging method. A bootstrap approach was used to assess the inherent variation in this estimated probability. RESULTS: The estimated probability of exceeding the threshold of 100 ng of furosemide/ml and urine specific gravity < 1.012 was approximately 0% between 4.0 and 5.5 hours after IV administration of 250 mg of furosemide/horse, and ranged from 0 to 1% between 4 and 5.5 hours after IV administration of 500 mg of furosemide/horse. The probability of a horse being falsely identified as in violation of regulatory concentrations was inversely associated with time. CONCLUSIONS AND CLINICAL RELEVANCE: Coupling plasma furosemide concentration with urine specific gravity testing will greatly reduce the chance that some horses are misclassified as being in violation of regulatory concentrations.

Role of laparoscopic assisted vaginal hysterectomy in gynecology.

One hundred and thirty laparoscopic assisted vaginal hysterectomies (LAVH) were performed at Chang Gung Memorial Hospital. All hysterectomies were for indications of the uterus, endometriosis, and extensive adhesions. Some of the patients also underwent concomitant procedures including unilateral or bilateral salping-oophorectomy, vaporization and/or excision of endometriosis, lysis and/or excision of adhesions. Kleppinger bipolar forceps were used for large vessel hemostasis and excision of adhesions in all the patients. CO2 laser was used for vaporization and excision of endometriosis. The complication rate was 10.0%. This included febric morbidity, intraoperative bladder injury, partial small bowel obstructions and thermal injury of the sigmoid colon. Four patients required laparotomy either to complete the procedure or to manage the complications. The mean blood loss was 160 ml and the mean hospital stay was 2.2 days. The mean operating time was 148 minutes and the mean age of the patients was 42.3 years. Two weeks after surgery, the majority of the patients were permitted to drive and resume normal nonstrenuous physical activity. The majority of the surgeries were videotaped. The study demonstrates that a hysterectomy can be safely performed laparoscopically by the well trained laparoscopic surgeon, resulted in reduced surgical morbidity, blood loss, postoperative discomfort and pain, shortened hospital stay and recovery.

Absorption of irrigating fluid during transcervical resection of endometrium--a report of two cases.

It has been recognized for many years that the use of hypotonic solution for the irrigation of the bladder cavity during transurethral resection of the prostate (TURP) may result in hyponatremia and water intoxication due to rapid and excessive absorption of the solution from the exposed prostatic bed, the clinical manifestation of which is termed "TURP syndrome". A similar condition termed "female TURP syndrome" following hysteroscopic transcervical endometrial resection (TCR) has been reported. Since the frequency of TCR continues to increase the increased rate of "TCR syndrome" would come in its wake. Here, we present two cases who developed severe hyperglycemia and hyponatremia while underwent TCR with 10% dextrose in water as the irrigation fluid and the same time emphasize the potential risk of this complication.

Development of signature-tagged mutagenesis in Burkholderia pseudomallei to identify genes important in survival and pathogenesis.

Burkholderia pseudomallei, the causative agent of melioidosis, is an important human pathogen in Southeast Asia and northern Australia for which a vaccine is unavailable. A panel of 892 double signature-tagged mutants was screened for virulence using an intranasal BALB/c mouse model of infection. A novel DNA tag microarray identified 33 mutants as being attenuated in spleens, while 6 were attenuated in both lungs and spleens. The transposon insertion sites in spleen-attenuated mutants revealed genes involved in several stages of capsular polysaccharide biosynthesis and DNA replication and repair, a putative oxidoreductase, ABC transporters, and a lipoprotein that may be important in intercellular spreading. The six mutants identified as missing in both lungs and spleens were found to have insertions in recA involved in the SOS response and DNA repair; putative auxotrophs of leucine, threonine, p-aminobenzoic acid, and a mutant with an insertion in aroB causing auxotrophy for aromatic compounds were also found. Murine challenge studies revealed partial protection in BALB/c mice vaccinated with the aroB mutant. The refined signature-tagged mutagenesis approach developed in this study was used to efficiently identify attenuating mutants from this highly pathogenic species and could be applied to other organisms.

Solid-phase extraction-fluorimetric high performance liquid chromatographic determination of domoic acid in natural seawater mediated by an amorphous titania sorbent.

The feasibility of using sol-gel amorphous titania (TiO2) as a solid-phase sorbent for the pre-concentration of domoic acid (DA), a potent amnesic shellfish poisoning (ASP) toxin, directly from seawater was explored. The sol-gel titania material is able to adsorb DA from seawater, via the formation of ester-linkage between the carboxylic moieties of DA and the Ti-OH groups on the sorbent surface, at low pH and desorb it at high pH. The chemisorption process is not significantly interfered by the seawater matrix. The optimum pH values for the adsorption and desorption of DA were found to be pH 4 and 11, respectively. The optimal sorbent loading for the batch-type solid-phase extraction of DA was 0.67 mg-TiO2 ng-DA(-1) and adsorption equilibrium was achieved in 2 h at room temperature. The desorbed DA in 500 microL of 0.1 M alkaline borate buffer can be directly derviatized by 4-fluoro-7-nitro-2,1,3-benzoxadiazole (NBD-F) in aqueous media for fluorimetric HPLC quantification. Analyte recovery, repeatability and detection limit of this titania SPE-fluorimetric HPLC determination are 89%, 6.2% and 120 pg-DA mL(-1) (n=7, P<0.05), respectively, for a sample volume of 30 mL. This titania SPE technique should also be applicable to the pre-concentration of other polar carboxylate- and phosphonate-containing biomolecules and pharmaceuticals in complex and interfering environmental sample matrices.

Pulmonary edema during ritodrine tocolysis--a case report.

A case of maternal pulmonary edema is presented as a late complication after intravenous administration of ritodrine in combination with dexamethasone for the suppression of premature uterine contraction and for the stimulation of fetal lung maturity. Swan-Ganz catheterization showed normal pulmonary capillary wedge pressures. Two-dimensional echocardiography disclosed good ventricular performance. The patient recovered very soon in 2 days post termination of pregnancy. Relative fluid overload might probably be responsible for the development of pulmonary edema in this case.