Web alert. Neural control.

A selection of World Wide Web sites relevant to reviews published in this issue of Current Opinion in Neurobiology.

Selective embryo reduction in a heterotopic pregnancy using potassium chloride injection resulting in a hematosalpinx.

OBJECTIVE: To incorporate conservative management of a heterotopic pregnancy using injection of KCl into the ectopic pregnancy (EP). DESIGN: A retrospective case report. SETTING: A patient referred to an academic institution in the division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, incorporating the ultrasound (US) and operating room facilities. INTERVENTION(S): Using US as a guide, KCl was injected into the chorionic cavity of an EP. MAIN OUTCOME MEASURE(S): Resolution of ectopic gestational tissue with resultant hematosalpinx requiring exploratory laparotomy. Uncomplicated prenatal course of intrauterine pregnancy. RESULT(S): Injection of KCl into the chorionic cavity of EP resulting in resolution of gestational tissue but complicated by hematosalpinx in the fallopian tube. CONCLUSION(S): Selective embryo reduction of a tubal heterotopic pregnancy remains a viable therapeutic option.

Midcycle increase of prolactin seen in normal women is absent in subjects with unexplained infertility.

OBJECTIVE: To compare the bioactive and immunoactive PRL in normal and unexplained infertility subjects. DESIGN: Prospective study. SETTING: Department of Obstetrics and Gynecology, Wayne State University and The University of Michigan. PATIENT(S): Twelve normal, fertile women compared with 12 patients with unexplained infertility. INTERVENTION(S): Serum samples were obtained across the menstrual cycle and for each subject, 5 pools were prepared by combining serum aliquots from the early follicular, late follicular, midcycle, and midluteal and late luteal phases of the cycle. MAIN OUTCOME MEASURE(S): Niobium lymphoma cell bioassay and an immunoradiometric assay were used to quantitate PRL. RESULT(S): A midcycle increase in PRL was seen in controls by both assays and these levels were greater compared with other cycle stages. Comparison of midcycle PRL between groups showed differences only between bioactive PRL (34.2 +/- 8.3 versus 19.2 +/- 3.4 ng/mL [conversion factor to SI unit, 1.00]). The ratios between bioactive and immunoactive PRL were comparable. Significant correlation between bioactive and immunoactive PRL was seen for both control (r = 0.616) and unexplained infertility (r = 0.660) groups. CONCLUSION(S): The midcycle elevations of bioactive and immunoactive PRL seen in normal women were absent in women with unexplained infertility. This alteration in PRL dynamics may be a part of subtle differences in the reproductive hormone profile of women with unexplained infertility compared with their fertile counterparts.

Method for setting total graft force and load sharing in augmented ACL grafts.

The objective of this study was to develop a method for obtaining a controllable and reproducible immediate postoperative mechanical state in a knee with an anterior cruciate ligament (ACL) reconstruction. This method, called the force-setting technique, was demonstrated using a composite graft consisting of the middle third of the patellar tendon with bone blocks (PT) and the ligament augmentation device (LAD). The total graft force was set to match the force in the intact ACL at 30 degrees flexion with the knee under the same standardized external load, while at the same time the load sharing between the biologic and augmentation components was controlled. The total graft force was set to match the ACL force three separate times in each knee, with ratios of load sharing set at the following levels: 50% PT-50% LAD, 25% PT-75% LAD, and 75% PT-25% LAD. ACL, PT, LAD, and collateral forces were measured using buckle transducers, and three-dimensional knee motion was measured using an instrumented spatial linkage as 90 N anteriorly directed tibial loads were applied to eight specimens at 0 degree, 30 degrees, 60 degrees, and 90 degrees flexion with an intact ACL, an excised ACL, and the three load-sharing reconstruction states. The total graft force could be consistently set to within an average of 2% of the intact ACL force at 30 degrees flexion, and load sharing between the graft segments could be set to within an average of 5.1% of the desired ratio at 30 degrees.(ABSTRACT TRUNCATED AT 250 WORDS)

Factors affecting graft force in surgical reconstruction of the anterior cruciate ligament.

The effect of the maximum unloaded graft length (Lo) and femoral fixation hole location on graft force with the knee under anteriorly directed tibial loads was measured in five fresh cadaver knees with a reconstruction of the anterior cruciate ligament (ACL). The reconstruction was performed using a composite graft consisting of the semitendinosus and gracilis tendons augmented with the Kennedy ligament augmentation device (LAD). Buckle transducers were used to measure ligament and graft forces. The total graft force was adjusted to match the intact ACL at 30 degrees flexion using a force-setting method so that a standardized reference configuration could be repeatedly obtained. The graft force was highly sensitive to Lo, typically changing by 50% with a change in Lo of 3 mm. Variation in femoral hole location of 5 mm anterior, posterior, proximal, and distal to the anatomic position produced changes in graft force, particularly at 60 degrees and 90 degrees flexion; however, these changes were not statistically significant. The effect of femoral hole location varied considerably between knees. This variability makes predicting proper hole placement difficult, and suggests the need to adjust each knee at surgery to account for this variable femoral hole position sensitivity.

Graft force-setting technique in reconstruction of the anterior cruciate ligament.

The objective of this work was to present a method for controlling the mechanical state of the knee during graft fixation in an ACL reconstruction; that is, adjusting the unloaded length of the graft at the time of fixation so that the force-carrying characteristics of the graft match that of the intact ACL, when the normal and reconstructed knees are subjected to the same external load. To demonstrate the new method, an experimental knee testing system was used to measure ligament and graft forces with buckle transducers, as external loads were applied to five fresh knee specimens with a pneumatic load apparatus. ACL and collateral ligament force data were collected as anteriorly directed loads of 90 N (20 pounds) were applied at 0 degrees, 30 degrees, 60 degrees, and 90 degrees of flexion in the normal intact knee and the same knee following ACL excision. A composite graft was prepared, consisting of distally based semitendinosus and gracilis autogenous tissue augmented with the Kennedy Ligament Augmentation Device. Femoral fixation was obtained using a fixation plug that was inserted through the lateral femoral condyle. With a 90 N anterior tibial load applied at 30 degrees of flexion and a single buckle transducer measuring the total composite graft force, the graft length was varied using the fixation plug until the force matched that seen by the intact ACL under the same loading condition. The graft was then clamped in the fixation plug and the anterior load sequence at the four flexion angles was applied to this reconstructed knee state.(ABSTRACT TRUNCATED AT 250 WORDS)

Load sharing and graft forces in anterior cruciate ligament reconstructions with the Ligament Augmentation Device.

Buckle transducers were used to directly measure load sharing and overall force in three segment (semitendinosus, gracilis, Ligament Augmentation Device) and two segment (patellar tendon, LAD) composite ACL grafts during the application of anteriorly directed loads to a series of five fresh knee specimens with a pneumatic load apparatus. The total graft forces generated in the two segment and three segment composite reconstructions during this immediate postoperative state were highly variable when compared to the normal ACL in each specimen, and were irreproducible among the five specimens. Load sharing among the graft components occurred and was also variable in both reconstructions, with this variation being greater in the three segment graft. The LAD carried an average of 45% of the total graft force in the three segment graft and 28% in the two segment graft. Further work is required to clarify the source of the variability in the total graft force and load sharing observed in this study.

Well-differentiated endometrial adenocarcinoma in an infertility patient with later conception. A case report.

BACKGROUND: The incidence of well-differentiated endometrial adenocarcinoma in reproductive-age women is approximately 5%. When the women desires to retain her future fertility in light of this diagnosis, choices of surgery vs. medical therapy may present a dilemma for both the physician and patient. CASE: A young infertility patient with well-differentiated endometrial adenocarcinoma conceived by ovulation induction and intrauterine insemination after medical therapy. She subsequently delivered vaginally, and follow-up dilatation and curettage revealed no evidence of recurrent carcinoma. CONCLUSION: This case illustrates that with close observation by endometrial sampling for histologic diagnosis and follow-up, medical therapy can be an option for treating this condition to allow future fertility. The patient must be extensively counseled, however, concerning the nearly 33% chance of progression or recurrence of disease. One must also stress the importance of frequent evaluation of symptoms and endometrial pathology postpartum, with endometrial sampling as indicated and discussion of definitive surgical therapy once fertility is no longer desired.

Pediatric and Adolescent Gynecology experience in academic and community OB/GYN residency programs in Michigan.

OBJECTIVES: The purpose of this study is to assess training in Pediatric and Adolescent Gynecology (PAG) at the Obstetrics and Gynecology (OB/GYN) resident level. SETTING: Two large Michigan programs were studied: a university-based, inner-city program, and a suburban, community-based program. Seventy-one questionnaires were distributed to the residents, and descriptive and inferential analysis of answers to demographic, training, attitude, and knowledge-based questions regarding PAG was performed. RESULTS: Sixty-one questionnaires were returned, a response rate of 86%. The majority of respondents reported no PAG rotations or clinics and recalled limited didactic sessions with only 0-2 lectures. Ninety-eight percent of university residents and 94% of community residents requested more PAG training. Comfort levels about PAG issues were assessed on a 5 point scale (1 = low, 5 = high comfort); university residents scored 3.7 with pediatric patients and 4.4 with adolescents, and community residents scored 4.0 with the pediatric age group and 4.3 with adolescents. However, both groups responded with familiarity to knowledge based questions only 61% of the time. CONCLUSIONS: OB/GYN residents in both academic and community programs report little experience and scant training in PAG but express interest in obtaining the skills and information needed. It is concerning that residents lack the basic knowledge that is required for the routine daily care of this patient population. More emphasis needs to be placed on these issues in OB/GYN residency training programs.

Gonococcal infection in cerebrospinal fluid and the presence of a ventriculoperitoneal shunt.

BACKGROUND: Neisseria gonorrhoeae is one of the most common organisms associated with pelvic disease in a woman of reproductive age. CASE: We present an unusual case of cerebrospinal fluid infection with N. gonorrhoeae in a woman with a ventriculoperitoneal shunt who complained of abdominal pain. Her shunt was removed and after adequate antibiotic therapy, it was re-inserted. CONCLUSION: Sexually active women, especially those with ventriculoperitoneal shunts, should be encouraged to use a barrier method of contraception, and should have a pelvic examination as part of their evaluation when they present with complaints of abdominal pain.

An association between precocious puberty and fragile X syndrome?

STUDY OBJECTIVE: To determine the FMR1 gene status in a 10-year, 10-month-old girl with a history of precocious puberty and a family history of fragile X syndrome. DESIGN: Case report. SETTING: The outpatient facility of the Division of Adolescent Medicine and the Division of Genetic and Metabolic Disorders at Children's Hospital of Michigan and the Medical Genetics and Birth Defects Center of Henry Ford Hospital, Detroit, Michigan. PARTICIPANT: A 10-year, 10-month-old girl with a history of precocious puberty. INTERVENTION: Evaluation for menorraghia, DNA extraction, and fragile X gene analysis of blood samples from the patient and her mother. MAIN OUTCOME MEASURES: Identification of a full mutation in the FMR1 gene. RESULTS: Southern blot analysis of the FMR1 gene identified a full mutation in the daughter with approximately 750 repeats of the CGG sequence. Methylation studies showed that the full mutation was completely methylated. FMR1 DNA studies on her mother identified a premutation of approximately 100 repeats. CONCLUSIONS: This report identifies a young girl with a history of precocious puberty and fragile X syndrome. It is also the first report of molecular genetic FMR1 studies in a female with precocious puberty. A possible association between the two conditions is suggested and warrants further investigation.

The biochemical ecology of Biomphalaria glabrata, a snail host of Schistosoma mansoni: short chain carboxylic and amino acids as phagostimulants.

1. A buccal mass olfactometer was used to investigate the responses of the fresh-water pulmonate snail Biomphalaria glabrata to carboxylic and amino acids. 2. The snails proved very discriminating as only 6 (14.6%) of the 41 chemical species tested were effective as phagostimulants. These are ranked as follows in order of potency:- butanoate greater than propanoate greater than D-malate greater than 2-hydroxybutanoate = L-tartrate = L-aspartate. 3. The structure-activity relationships of the active compounds, and their significance to the ecology and control of the snails are discussed.

Coiled-coil assembly by peptides with non-heptad sequence motifs.

BACKGROUND: The seven-residue heptad repeat is the accepted hallmark of coiled coils. In extended filamentous proteins, however, contiguous patterns of heptads are often disrupted by 'skips' and 'stammers'. The structural consequences and roles of these digressions are not understood. RESULTS: In a cytoskeleton protein from Giardia lamblia, heptads flank eleven-residue units (hendecads) to give a 7-11-7 motif that dominates the sequence. Synthetic peptides made to the consensus sequence of this motif fold in solution to fully helical, parallel dimers. Both the sequence pattern and these experimental data are consistent with the coiled-coil model. We note that breaks in other extended coiled coils can also be reconciled by hendecad insertions. CONCLUSIONS: The heptad paradigm for the coiled coil must be expanded to include hendecads. As different combinations of heptads and hendecads will give different overall sequence motifs, we propose that these provide a mechanism to promote cognate protein pairings during the folding of extended coiled coils in the cell.

Urinary beta-core fragment as a predictor of abnormal pregnancy at 4-6 weeks' gestation.

Currently, transvaginal ultrasound and serial serum beta-hCG measurements are used to differentiate normal versus abnormal gestations in the first trimester of pregnancy. These techniques have been found to be ineffective when the gestations are earlier than 6 weeks. This study was conducted to determine if urinary beta-core fragment, the urine degradation product of beta-hCG, could be used to distinguish normal from abnormal gestations between 4 and 6 weeks. Urine samples were obtained from 27 patients on initial presentation to the emergency room or outpatient settings with gestations at 4-6 weeks by sure last menstrual period. The urine was then frozen at -40 degrees C and sent for beta-core assay analysis. Eighteen women with normal intrauterine pregnancies and nine abnormal pregnancies, including ectopics and spontaneous abortions, were studied. Pearson correlations were performed with a p < 0.05 considered significant. In the normal gestations, there was a positive correlation between beta-core fragment and gestational age at 4-6 weeks (r = 0.461, p < 0.05). This correlation was not evident in abnormal gestations (r = 0.360, p = 0.34). In early pregnancy, beta-core fragment correlates positively with gestational age which is not apparent in abnormal counterparts. This finding suggests that urinary beta-core fragment may be a promising marker to differentiate normal early pregnancies from abnormal gestations.

Deletion in HCDR3 rescues T15 antibody mutants from a secretion defect caused by mutations in HCDR2.

We recently described mutants of the murine anti-phosphocholine Ab T15, with changes in heavy chain complementarity determining region 2 (HCDR2) that caused loss of secretion. Surprisingly, the T15 HCDR2 mutations did not alter secretion when placed into the related anti-phosphocholine Ab D16, which differs from T15 only in HCDR3 and light (L) chain. Here, we exploit the differences between these two Abs to assess the basis of the secretion defect. The T15 L chain is not secreted in the absence of heavy (H) chain. In contrast, D16 L chain is secreted in the absence of H chain, as are most L chains. We co-expressed the T15 wild-type (wt) and mutant H chains with the D16 L chain, as well as with another secreted L chain, J558L. The mutant H chains were not secreted when expressed with either heterologous L chain. These results establish that the T15 L chain is not uniquely associated with the defect. The T15 and D16 Abs also differ in HCDR3 length in that D16 lacks four amino acid residues (Ser99, Ser100, Tyr100a, Trp100b) present in T15. We deleted these four residues from T15 wt and mutant H chains. Secretion of T15 wt was unaffected by the deletion, but shortening HCDR3 restored secretion in the HCDR2 mutants regardless of L chain association. Together these data demonstrate that both the HCDR2 and HCDR3 domains contain structural information that may affect the secretion competence of Abs.