Mode of delivery and subsequent fertility.

STUDY QUESTION: When compared with vaginal delivery, is Cesarean delivery associated with reduced childbearing, a prolonged inter-birth interval or infertility? SUMMARY ANSWER: Women whose first delivery was by Cesarean section were not significantly different from those who delivered vaginally with respect to subsequent deliveries, inter-birth interval or infertility after delivery. WHAT IS ALREADY KNOWN: Some studies have suggested that delivery by Cesarean section reduces subsequent fertility, while others have reported no association. STUDY DESIGN, SIZE, DURATION: This was a planned secondary analysis of the Mothers' Outcomes After Delivery study, a longitudinal cohort study. This analysis included 956 women with 1835 deliveries, who completed a study questionnaire at 6-11 years (median [interquartile range]: 8.1 [7.1, 9.8]) after their first delivery. PARTICIPANTS/MATERIALS, SETTING, METHODS: Exclusion criteria regarding the first birth were: maternal age <15 or >50 years, delivery at <37 weeks gestation, placenta previa, multiple gestation, known fetal congenital abnormality, stillbirth, prior myomectomy and abruption. Of the 956 women included, the first delivery was by Cesarean section for 534 women and by vaginal birth for 422 women. Infertility was self-reported. To compare maternal characteristics by mode of first delivery, P-values were calculated using Fisher's exact test or Pearson's χ(2) test for categorical variables and a Kruskall-Wallis test for continuous variables. We also considered whether, across all deliveries to date, a prior Cesarean is associated with decreased fertility. In this analysis, self-reported infertility after each delivery (across all participants) was considered as a function of one or more prior Cesarean births, using generalized estimating equations to control for within-woman correlation. MAIN RESULTS AND THE ROLE OF CHANCE: No differences were observed between the Cesarean and vaginal groups (for first delivery) with respect to infertility after their most recent delivery (7 versus 6%, P = 0.597), the interval between their first and second births (30.8 versus 30.6 months, P = 0.872), or multiparity (75 versus 76%, P = 0.650). Across all births, a history of Cesarean delivery was not significantly associated with infertility (odds ratio [OR], 0.90; 95% confidence interval [CI], 0.64-1.26). Women who reported infertility prior to their first delivery were significantly more likely to report infertility after each subsequent delivery (OR, 5.16; 95% CI, 3.60-7.39). LIMITATIONS, REASONS FOR CAUTION: Due to the use of self-reported infertility, the fertility status of some participants may be misclassified. Also, the small sample size may result in insufficient power to detect small differences between groups. Finally, a relatively high proportion of our participants were over age 35 at the time of first delivery (26%) and highly educated (37% with graduate degrees), which may indicate that our population may not be generalizable. WIDER IMPLICATIONS OF THE FINDINGS: While some prior studies have shown decreased family size among women who deliver by Cesarean, our results suggest that the rate of infertility is not different after Cesarean compared with vaginal birth. Our findings should be reassuring to women who deliver by Cesarean section. STUDY FUNDING/COMPETING INTERESTS: This study was funded by the US National Institutes of Health (NIH, R01-HD056275). No competing interests are declared. TRIAL REGISTRATION NUMBER: N/A.

Etiology of post-uterosacral suspension neuropathies.

INTRODUCTION AND HYPOTHESIS: The goal of our investigation was to find a neurological explanation for neuropathies reported following some uterosacral ligament suspension (USLS) [2-3]. METHODS: We dissected the neural structures beneath the USL in seven female, adult, embalmed cadavers. We made a literature review to determine the spinal nerve sensory fiber composition of each exposed neural structure and the dermatome(s) that it innervates. We then compared anticipated sensory neuropathies for each neural structure with neuropathies following USLS to determine which neural structure entrapment could explain the reported symptoms. RESULTS: Several neural structures located beneath the uterosacral ligament (USL) are vulnerable to suture entrapment during USLS. Anticipated clinical outcomes of entrapments are discussed. CONCLUSIONS: Entrapment of S2 sensory fibers in the second trunk of the sacral plexus or in the intrapelvic portion of the sciatic nerve is the most plausible etiology for reported neuropathies following USLS.

Identification, isolation and characterization of impurities of clindamycin palmitate hydrochloride.

Clindamycin palmitate hydrochloride is a water soluble hydrochloride salt of the ester of clindamycin and palmitic acid. It is inactive in vitro, rapid in vivo hydrolysis converts this compound to the antibacterially active clindamycin. Total 12 impurities at levels ranging from 0.05% to 0.5% were detected by isocratic reverse-phase high performance liquid chromatography (HPLC) using RI detector. The molecular weights of impurities were determined by LC-MS analysis. Two impurities were starting materials and the remaining impurities were isolated from crude samples/enriched mother liquors using reverse-phase preparative HPLC. Based on the spectral data the structures of these impurities were characterized as, clindamycin palmitate sulphoxides alpha-/beta-isomers (impurity I); clindamycin laurate (impurity II); lincomycin palmitate (impurity III); clindamycin myristate (impurity IV); epiclindamycin palmitate (impurity V); clindamycin palmitate 3-isomer (impurity VI); clindamycin pentadecanoate (impurity VII); clindamycin B-palmitate (impurity VIII); clindamycin heptadecanoate (impurity IX) and clindamycin stearate (impurity X). Structural elucidation of all impurities by spectral data ((1)H NMR, (13)C NMR, MS and IR) and formation of these impurities have been discussed in detail.

Identification, isolation, synthesis and characterization of impurities of quetiapine fumarate.

In the process for the preparation of quetiapine fumarate (1), six unknown impurities and one known impurity (intermediate) were identified ranging from 0.05-0.15% by reverse-phase HPLC. These impurities were isolated from crude samples using reverse-phase preparative HPLC. Based on the spectral data, the impurities were characterized as 2-[4-dibenzo[b,f][1,4]thiazepine-11-yl-1 -piperazinyl]1 -2-ethanol (impurity I, desethanol quetiapine), 11-[(N-formyl)-1-piperazinyl]-dibenzo[b,f][1,4]thiazepine (impurity II, N-formyl piperazinyl thiazepine), 2-(2-hydroxy ethoxy)ethyl-2-[2-[4-dibenzo[b,f][1,4]thiazepine-11- piperazinyl-1-carboxylate (impurity III, quetiapine carboxylate), 11-[4-ethyl-1-piperazinyl]dibenzo [b,f][1,4] thiazepine (impurity IV, ethylpiperazinyl thiazepine), 2-[2-(4-dibenzo[b,f][1,4]thiazepin-11-yl-1-piperazinyl)ethoxy]1-ethyl ethanol [impurity V, ethyl quetiapine), 1,4-bis[dibenzo[b,f][1,4]thiazepine-11-yl] piperazine [impurity VI, bis(dibenzo)piperazine]. The known impurity was an intermediate, 11-piperazinyldibenzo [b,f][1,4]thiazepine (piperazinyl thiazepine). The structures were established unambiguously by independent synthesis and co-injection in HPLC to confirm the retention times. To the best of our knowledge, these impurities have not been reported before. Structural elucidation of all impurities by spectral data (1H NMR, 13C NMR, MS and IR), synthesis and formation of these impurities are discussed in detail.

Identification, isolation and characterization of potential degradation product in risperidone tablets.

One unknown impurity (degradation product) present at a level below 0.1% in the initial samples increased to a level of 0.5% in 6M/40 degrees C/75% RH stability samples of risperidone tablets was detected by gradient reverse-phase high-performance liquid chromatography (HPLC). This impurity was isolated using reverse-phase preparative liquid chromatography. Based on the spectral data the structure of this impurity is characterized as 3-[2-[4-[6-fluoro-1,3-benzoxazol-2-yl]piperidin-1-yl]ethyl]-2-methyl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a] pyrimidin-4-one. Structural elucidation of this impurity by spectral data ((1)H NMR, (13)C NMR, DEPT, MS and IR), formation and mechanism has been discussed in detail.

Impurity profile study of zaleplon.

Zaleplon is a pyrazolopyrimidine derivative and possesses sedative and hypnotic properties. Seven unknown impurities in zaleplon bulk drug at levels below 0.1% were detected by reverse-phase high performance liquid chromatography (HPLC). The starting material, 3-amino-4-cyanopyrazole and an intermediate, N-[3-[3-(dimethylamino)-1-oxo-2-propenyl]-phenyl]-N-ethylacetamide (DOPEA) were also present in the sample at a level below 0.1%. The molecular weights of impurities were determined by LC-MS analysis. These impurities were isolated from crude samples of zaleplon using reverse-phase preparative HPLC. Based on the spectral data the structures of these impurities were characterized as, N-(3-(3-(4-amino-2H-pyrazolo [3,4-d]pyrimidin-6-yl) pyrazolo[1,5-a] pyrimidin-7-yl)phenyl)-N-ethylacetamide (impurity I); N-[3-(3-carboxamidopyrazolo[1,5-a]pyrimidin-7-yl)phenyl]-N-ethylacetamide (impurity II); N-[3-(3-cyanopyrazolo[1,5-a]pyrimidin-7-yl)phenyl]acetamide (impurity III); N-[3-(3-cyanopyrazolo [1,5-a]pyrimidin-7-yl)phenyl]-N-methylacetamide (impurity IV); N-[3-(3-cyanopyrazolo[1,5-a] pyrimidin-5-yl)phenyl]-N-ethylacetamide (impurity V); N-[3-(3-cyanopyrazolo[1,5-a] pyrimidin-7-yl)phenyl]-N-ethylamine (impurity VI); N-[3-(3-cyano-6-[(E)-3-((N-ethyl-N-acetyl)amino)phenyl-3-oxoprop-1-enyl] pyrazolo[1,5-a]pyrimidin-7-yl) phenyl]-N-ethylacetamide (impurity VII). Structural elucidation of all impurities by spectral data ((1)H NMR, (13)C NMR, MS and IR) and formation of these impurities are discussed in detail.

Human babesiosis--a case report.

Babesiosis is an emerging, tick-transmitted, zoonotic disease caused by hematotropic parasites of the genus Babesia. Most cases of Babesial infections in humans have been acquired in temperate regions of the United States, Europe, France and England. A few cases of Babesiosis have been described in other parts of the world, including China, Taiwan, Egypt, South Africa, and Mexico.1,2 We report the first case of human Babesiosis, in a normosplenic, previously healthy individual from India.

Transcription defects induced by repeat expansion: fragile X syndrome, FRAXE mental retardation, progressive myoclonus epilepsy type 1, and Friedreich ataxia.

Fragile X mental retardation syndrome, FRAXE mental retardation, Progressive myoclonus epilepsy Type I, and Friedreich ataxia are members of a larger group of genetic disorders known as the Repeat Expansion Diseases. Unlike other members of this group, these four disorders all result from a primary defect in the initiation or elongation of transcription. In this review, we discuss current models for the relationship between the expanded repeat and the disease symptoms.

Early diagnosis of filarial pleural effusion.

This paper describes a case of pleural effusion due to filariasis. Microfilaria of Wucheraria bancrofti were detected in the pleural fluid on cytological examination. Treatment with diethylcarbamazine cleared the pleural effusion.

Do pessaries prevent the progression of pelvic organ prolapse?

Pessaries are used for the management of pelvic organ prolapse, but it is unknown whether a pessary will prevent progression of this condition. The purpose of this study was to describe the course of pelvic organ prolapse among women using a pessary for at least 1 year. Among 56 consecutive women fitted with a pessary, 19 (33.9%) continued its use under our care for at least 1 year. We compared baseline and follow-up examinations, using the Pelvic Organ Prolapse Quantitation examination system. At baseline, 16 (84.2%) had stage 3 or 4 prolapse. After 1 year we observed a significant improvement in the stage of disease ( P = 0.045, Wilcoxon signed rank test). Four women (21.1%, 95% confidence interval -0.2, 43.7%) had an improvement in stage. No women had worsening in stage of prolapse. These data suggest that there may be a therapeutic effect associated with the use of a supportive pessary.

Diagnosis of ureteral obstruction during complex urogynecologic surgery.

Intraoperative cystoscopy has been recommended to identify unsuspected bladder and ureteral injuries resulting from gynecologic surgery. We retrospectively reviewed 157 cases of complex urogynecologic procedures at our institution. Intraoperative cystoscopy revealed no bladder injuries. Five cases of unsuspected ureteral obstruction were identified (3.2%). One case of ureteral ligation was diagnosed and repaired intraoperatively. The remaining 4 cases were found to represent chronic ureteral obstruction resulting from pelvic organ prolapse (2 cases), ureteropelvic junction obstruction (1 case) and stenosis of the ureterovesical junction after transurethral resection (1 case). Intraoperative assessment required an average of 90 minutes. Our experience suggests that pre-existing ureteral obstruction may be more common than intraoperative injury. In selected populations, routine preoperative assessment of the ureters is indicated to simplify intraoperative evaluation.

Posthysterectomy vault eversion with a large retroperitoneal mass.

A woman with complete vaginal eversion was found to have a large pelvic mass, extending from the rectovaginal septum to the presacral space. This 66-year-old woman with posthysterectomy vaginal eversion complained of pelvic fullness. A pessary provided relief of the prolapse, but the symptom of fullness persisted. Physical examination did not identify a pelvic mass. Computed tomography (CT) and magnetic resonance imaging (MRI) demonstrated a 9 cm tumor of the rectovaginal septum, extending to the presacral space. At laparotomy the patient had a massive neurofibroma arising from the anterior rectal wall. This case is of interest because the complete vaginal prolapse obscured the diagnosis of this large pelvic tumor. CT and MRI were useful in identifying and characterizing the mass. To our knowledge, this is the first reported case of vaginal prolapse with a large pelvic mass.

Obstetric anal sphincter lacerations.

OBJECTIVE: To estimate the frequency of obstetric anal sphincter laceration and to identify characteristics associated with this complication, including modifiable risk factors. METHODS: A population-based, retrospective study of over 2 million vaginal deliveries at California hospitals was performed, using information from birth certificates and discharge summaries for 1992 through 1997. We excluded preterm births, stillbirths, breech deliveries, and multiple gestations. The main outcome measure was obstetric anal sphincter laceration (third and fourth degree). RESULTS: The frequency of anal sphincter lacerations was 5.85% (95% confidence interval [CI] 5.82, 5.88), decreasing significantly from 6.35% (95% CI 6.27, 6.43) in 1992 to 5.43% (95% CI 5.35, 5.51) in 1997 (P <.01). Using logistic regression analysis, we identified primiparity as the dominant risk factor (odds ratio [OR] for women with prior vaginal birth 0.15; 95% CI 0.14, 0.15). Birth weight over 4000 g was also highly significant (OR 2.17; 95% CI 2.07, 2.27). Lacerations occurred more often among women of certain racial and ethnic groups: Indian women (OR 2.5; 95% CI 2.23, 2.79) and Filipina women (OR 1.63; 95% CI 1.50, 1.77) were at highest risk. Episiotomy decreased the likelihood of third-degree lacerations (OR 0.81; 95% CI 0.78, 0.85), but increased the risk of fourth-degree lacerations (OR 1.12; 95% CI 1.05, 1.19). Operative delivery increased the risk of sphincter laceration, with vacuum delivery (OR 2.30; 95% CI 2.21, 2.40) presenting a greater risk than forceps delivery (OR 1.45; 95% CI 1.37, 1.52). CONCLUSION: Anal sphincter lacerations are strongly associated with primiparity, macrosomia, and operative vaginal delivery. Of the modifiable risk factors, operative vaginal delivery remains the dominant independent variable.

Deficiency of the 50 kDa dystrophin-associated-glycoprotein (adhalin) in an Indian autosomal recessive limb girdle muscular dystrophy patient : immunochemical analysis and clinical aspects.

Abnormalities of dystrophin are a common cause of muscular dystrophy and testing for dystrophin gene or protein has become a part of routine diagnostic evaluation of patients who present with progressive proximal muscle weakness, high serum creatine kinase concentrations, and histopathological evidence of a dystrophic process. Patients who have no dystrophin abnormalities are assumed to have autosomal recessive muscular dystrophy. In a family consisting of 5 sibs, 2 mentally normal brothers presented with abnormal gait and protrusion of chest and hips. Muscle biopsy from one of them showed dystrophic changes and reduced patchy binding of dystrophin. No detectable deletion was observed in the patient's DNA and his brother with cDMD probes. Dystrophin associated proteins, beta-dystroglycan showed discontinuous immunostaining in the sarcolemma and alpha-sarcoglycan (adhalin) was totally absent, while beta-, gamma-, and delta-sarcoglycans were highly reduced. Immunoblot analysis showed dystrophin of normal molecular weight but of decreased quantity, beta-dystroglycan was reduced by about 37% while alpha-sarcoglycan was completely absent. This study is a first attempt for a systematic clinical, genetic and molecular investigation of the autosomal recessive LGMD in India.

Fungal culture findings in cyclic vulvitis.

OBJECTIVE: To estimate the prevalence of fungal infection in cyclic vulvitis. METHODS: We retrospectively reviewed 40 cases of cyclic vulvitis. We examined the historic characteristics, physical findings, and laboratory results in this population, including the results of potassium hydroxide preparations of vaginal secretions and fungal cultures. RESULTS: The median age was 32 years and the mean duration of symptoms was 3.8 years. Thirty women (75%) reported prior antifungal therapies. Fungal cultures were positive in 24 of 39 (61.5%). Candida albicans was the species isolated in 13 of 24 cases (54%). Potassium hydroxide wet mounts contained evidence of fungal infection in 15 of 37 cases (40.5%). The sensitivity of the potassium hydroxide preparation was only 61%. Potassium hydroxide preparations were more sensitive when the species isolated was C albicans. CONCLUSIONS: Many women with cyclic vulvitis have positive vaginal fungal cultures. Potassium hydroxide preparations of vaginal secretions are not sufficiently sensitive to exclude fungal infection in this setting, possibly because of the relatively high incidence of fungal species other than C albicans. Fungal culture should be considered in the evaluation of women with recurrent episodes of vulvar discomfort, even when potassium hydroxide wet mounts do not contain fungal elements.

Stress urinary incontinence at rest.

We retrospectively identified 37 cases in which urinary incontinence occurred at rest during urodynamic testing in the absence of a coincident detrusor contraction or urethral relaxation. This phenomenon, genuine stress incontinence at rest, was observed during 9.6% of multichannel cystometrograms performed at our institution. The observed urine loss occurred at bladder volumes between 145 ml and 800 ml. Loss occurred with bladder overdistension (overflow incontinence) in only 3 subjects (8%). Decreased bladder compliance was observed in 11 (30%) and decreased outlet resistance was demonstrated in 24 (65%). Our findings suggest that genuine stress incontinence at rest is relatively common in a referred population of incontinent women. This phenomenon is associated with impaired urethral function and/or decreased bladder compliance.

Erosion of a fascial sling into the urethra.

When synthetic materials are used for the construction of pubovaginal slings, urethral erosions may occur. This complication has not been reported with fascial slings. We present a case of a 34-year-old woman who underwent a pubovaginal sling procedure using rectus fascia. After 10 weeks of urinary retention, urethroscopy identified an erosion of the sling at the midurethra. Surgical revision restored normal voiding without recurrent stress incontinence. Although urethral erosions have been reported with synthetic suburethral slings, this case suggests that erosions can also occur with fascial slings. Careful positioning and minimal tension on the sling arms may minimize this risk.

Banked human fascia lata for the suburethral sling procedure: a preliminary report.

OBJECTIVE: To report our initial experience with allogenic (human cadaver donor) fascia lata for the suburethral sling procedure. METHODS: Allogenic fascia lata for the suburethral sling procedure has been used in our practice since July 1994. Fascial grafts were obtained from licensed tissue banks. Women who underwent this procedure were followed prospectively to determine the incidence of perioperative complications, the incidence of local wound complications at the sling insertion site, and the subjective and objective cure rates. RESULTS: Sixteen women underwent the suburethral sling procedure with allogenic fascia. Fourteen had genuine stress urinary incontinence and two required replacement of a previously placed synthetic graft because of chronic infection. Follow-up ranged from 6 months to 1 year. No patient developed sinus tract formation or persistent granulation tissue. Two of 16 patients (12%) developed abdominal wound infections, which resolved with local care. The mean duration of postoperative bladder drainage was 29 days. One patient continued to require intermittent catheterization at 187 days. Among the 14 women with preoperative genuine stress incontinence, the subjective cure rate was 86% and the objective cure rate was 79%. The two patients who required replacement of a chronically infected synthetic graft remained subjectively continent. CONCLUSIONS: These preliminary data suggest that allogenic fascia lata is an acceptable material for the suburethral sling procedure. This material may be considered as an alternative to autologous fascia, which must be harvested from the patient intraoperatively, and to synthetic materials, which have been associated with local complications in up to 40% of cases.

Protecting the pelvic floor: obstetric management to prevent incontinence and pelvic organ prolapse.

OBJECTIVES: To review the literature regarding the effects of childbirth on the muscles, nerves, and connective tissue of the pelvic floor, review the evidence to support an association between childbirth and anal incontinence, urinary incontinence, and pelvic organ prolapse; and present recommendations for the prevention of these sequelae. DATA SOURCES: Sources were identified from a MEDLINE search of English-language articles published from 1984 to 1995. Additional sources were identified from references cited in relevant research articles. METHODS OF STUDY SELECTION: We studied articles on the following topics: anatomy of the pelvic floor association of childbirth with neuromuscular injury, biomechanical and morphologic alterations in muscle function, and connective tissue structure and function; the long-term effects of childbirth on continence and pelvic organ support; and the effects of obstetric interventions on the pelvic floor. TABULATION, INTEGRATION, AND RESULTS: Articles were reviewed and summarized. An overview of the structure and function of the pelvic floor was developed to provide a context for subsequent data. Childbirth was found to be associated with a variety of muscular and neuromuscular injuries of the pelvic floor that are linked to the development of anal incontinence, urinary incontinence, and pelvic organ prolapse. Risk factors for pelvic floor injury include forceps delivery, episiotomy, prolonged second-stage of labor, and increased fetal size. Cesarean delivery appears to be protective, especially if the patient does not labor before delivery. CONCLUSION: The pelvic floor plays an important role in continence and pelvic organ support. Obstetricians may be able to reduce pelvic floor injuries by minimizing forceps deliveries and episiotomies, by allowing passive descent in the second stage, and by selectively recommending elective cesarean delivery.