Pubic arch angle in prolonged second stage of labor: clinical significance.

OBJECTIVE: To evaluate the clinical significance of the pubic arch angle (PAA) measured by transperineal ultrasound during prolonged second stage of labor. METHODS: We evaluated prospectively 62 women ≥ 37 weeks of gestation with failure to progress in the second stage of labor. Transperineal ultrasound (transverse plane) was used to measure the pubic arch angle. Correlations with fetomaternal characteristics, mode of delivery and perinatal outcome were evaluated. RESULTS: The mean PAA was 101.1° (± 13.1°; range, 80°-135°). We found a negative correlation with maternal age. Patients with an occipitotransverse fetal position had a significantly smaller angle compared with those with occipitoanterior positions (94.3° ± 5.5° vs. 103.2° ± 14.8°, P < 0.05), as did those with operative deliveries compared with those with spontaneous vaginal delivery (97.1° ± 11.5° vs. 110.1° ± 14.0°, P < 0.05). The prediction of operative delivery in prolonged second stage of labor by receiver-operating characteristics curve using PAA alone yielded an area under the curve of 0.75. The predicted probability for operative delivery increased as PAA decreased, with an odds ratio of 0.933 for each decrease in angle of 1°. CONCLUSION: Our study suggests a correlation between the PAA and mode of delivery in prolonged second stage of labor. This may be used as an adjunctive parameter when considering delivery mode.

Head progression distance in prolonged second stage of labor: relationship with mode of delivery and fetal head station.

OBJECTIVE: To evaluate the clinical significance of fetal head progression distance (HPD), measured by transperineal ultrasound, during prolonged second stage of labor. METHODS: In this prospective study, a single operator, who was blinded to the results of the digital examination, assessed using transperineal ultrasound women at ≥ 37 weeks of gestation with failure to progress in the second stage of labor. Patients had an empty urinary bladder and the examination was performed during maternal pushing. HPD was defined as the length of the line perpendicular to the infrapubic line that would connect it to the lowest part of the fetal bony skull. We analyzed associations between HPD and digital examination of fetal head station, fetomaternal characteristics, mode of delivery and perinatal outcome. RESULTS: Sixty-five patients in prolonged second stage of labor participated in the study. The overall mean HPD was 6.50 (± 1.35; 95% CI, 6.16-6.83) cm. No correlation was found between HPD and head position or mode of delivery, but HPD was positively correlated with fetal head station and neonatal head circumference measured after delivery. Logistic regression and receiver-operating characteristics curve analysis demonstrated no significant predictive value of HPD with respect to mode of delivery. CONCLUSION: Although HPD in prolonged second stage of labor could not predict mode of delivery, it may have a role as an ancillary tool for fetal head station assessment.

Induction of growth cone formation by transient and localized increases of intracellular proteolytic activity.

The formation of a growth cone at the tip of a transected axon is a crucial step in the subsequent regeneration of the amputated axon. During this process, the transected axon is transformed from a static segment into a motile growth cone. Despite the importance of this process for regeneration of the severed axon, little is known about the mechanisms underlying this transformation. Recent studies have suggested that Ca2+-activated proteinases underlay the morphological remodeling of neurons after injury. However, this hypothesis was never tested directly. Here we tested the ability of transient and localized increases in intracellular proteolytic activity to induce growth cone formation and neuritogenesis. Minute amounts of the proteinase trypsin were microinjected into intact axonal segments or somata of cultured Aplysia neurons, transiently elevating the intracellular protease concentration to 13-130 nM in the vicinity of the injection site. Such microinjections were followed by the formation of ectopic growth cones and irreversible neuritogenesis. Growth cones were not formed after external application of trypsin, microinjection of the carrier solution, or inactivated trypsin. Growth cone formation was not preceded by increases in free intracellular Ca2+ or changes in passive membrane properties, and was blocked by inhibitors of actin and tubulin polymerization. Trypsin-induced neuritogenesis was associated with ultrastructural alterations similar to those observed by us after axotomy. We conclude that local and transient elevations of cytoplasmic proteolytic activity can induce growth cone formation and neuritogenesis, and suggest that localized proteolytic activity plays a role in growth cone formation after axotomy.

Extracellular potassium ions mediate specific neuronal interaction.

The giant interneurons from the nerve system of the cockroach Periplaneta americana exhibit a peculiar reciprocal synaptic interaction. The synaptic potentials are not blocked by addition of 5 millimolar cobalt chloride and have an extrapolated reversal potential close to 0 millivolt. Hyperpolarizing current injected into one cell does not spread to the other. Intracellular injection of tetraethylammonium ions into one giant interneuron increases the duration of the action potential of the injected cell to 30 milliseconds and reduces the rise time and amplitude of the postsynaptic response recorded in the other giant interneuron. These results indicate that the interaction between the interneurons is not mediated by conventional chemical or electrotonic synapses.. All evidence points to generation of the potentials by localized increases in extracellular potassium concentrations as a consequence of firing of one neuron.

Membrane conductance and action potential of a regenerating axonal tip.

The electrical membrane properties of axotomized and regenerating giant axons from the nerve cord of the cockroach Periplaneta americana were studied. Immediately after axotomy there was a decrease in resting potential, input resistance, and action potential amplitude near the cut end. This decrease was followed by the disappearance of the sodium-dependent action potential; an increase in the resting membrane conductance to K+, Na+, and Ca2+; and the appearance of a calcium-dependent action potential.

Electrotonic coupling: effective sign reversal by inhibitory neurons.

Neurons in the buccal ganglia of Navanax inermis which control circumferential muscles of the pharynx showed typical electrotonic coupling when there was little synaptic activity in them. When there was much inhibitory activity, the effective sign of coupling was reversed; that is, hyperpolarization and depolarization of one cell caused depolarization and hyperpolarization of the others. A neural circuit explaining these results involes inhibitory neurons electronically coupled to and also inhibitory to the circumferential neurons that are themselves coupled. This circuit offers considerable flexibility for mediation of different activity patterns in this simple neuronal system.

Gluon fusion into Higgs pairs at NLO QCD and the top mass scheme.

We present the calculation of the full next-to-leading order (NLO) QCD corrections to Higgs boson pair production via gluon fusion at the LHC, including the exact top-mass dependence in the two-loop virtual and one-loop real corrections. This is the first independent cross-check of the NLO QCD corrections presented in the literature before. Our calculation relies on numerical integrations of Feynman integrals, stabilised with integration-by-parts and a Richardson extrapolation to the narrow width approximation. We present results for the total cross section as well as for the invariant Higgs-pair-mass distribution at the LHC, including for the first time a study of the uncertainty due to the scheme and scale choice for the top mass in the loops.

Real time imaging of calcium-induced localized proteolytic activity after axotomy and its relation to growth cone formation.

The emergence of a neuronal growth cone from a transected axon is a necessary step in the sequence of events that leads to successful regeneration. Yet, the molecular mechanisms underlying its formation after axotomy are unknown. In this study, we show by real time imaging of the free intracellular Ca2+ concentration, of proteolytic activity, and of growth cone formation that the activation of localized and transient Ca2+-dependent proteolysis is a necessary step in the cascade of events that leads to growth cone formation. Inhibition of this proteolytic activity by calpeptin, a calpain inhibitor, abolishes growth cone formation. We suggest that calpain plays a central role in the reorganization of the axon's cytoskeleton during its transition from a stable differentiated structure into a dynamically extending growth cone.

Acceleration of membrane recycling by axotomy of cultured aplysia neurons.

The rapid transition of a stationary axon into a motile growth cone requires the recruitment of membrane and its strategic insertion into the neurolemma. The source of membrane to support the initial rapid growth postaxotomy is not known. Using membrane capacitance measurements, we examined quantitative aspects of membrane dynamics following axotomy of cultured Aplysia neurons. Axotomy activates two processes in parallel: membrane retrieval and exocytosis. Unexpectedly, membrane retrieval is the dominant process in the majority of the experiments. Thus, while a growth cone is vigorously extending, the total neuronal surface area decreases. We suggest that the initial rapid extension phase of the newly formed growth cone postaxotomy is supported by a pool of intracellular membrane that is rapidly retrieved from the neurolemma.

Low mobility of the Ca2+ buffers in axons of cultured Aplysia neurons.

Cellular Ca2+ buffers determine amplitude and diffusional spread of neuronal Ca2+ signals. Fixed Ca2+ buffers tend to retard the signal and to lower the apparent diffusion coefficient (D(app)) of Ca2+, whereas mobile buffers contribute to Ca2+ redistribution. To estimate the impact of the expression of specific Ca2+-binding proteins or the errors in Ca2+ measurement introduced by indicator dyes, the diffusion coefficient De and the Ca2+-binding ratio kappa(e) of endogenous Ca2+ buffers must be known. In this study, we obtain upper bounds to these quantities (De < 16 microm2/s; kappa(e) < 60) for axoplasm of metacerebral cells of Aplysia california. Due to these very low values, even minute concentrations of indicator dyes will interfere with the spatiotemporal pattern of Ca2+ signals and will conceal changes in the expression of specific Ca2+-binding proteins, which in the native neuron are expected to have significant effects on Ca2+ signals.

Facilitatory and inhibitory transmitters modulate calcium influx during action potentials in aplysia sensory neurons.

Serotonin (5-HT) produces presynaptic facilitation and FMRFamide produces presynaptic inhibition in Aplysia sensory neurons. These effects may involve the modulation of Ca2+ influx into sensory neuron terminals during action potentials. Here, we have used the Ca2+ indicator dye fura-2 to monitor directly the effects of 5-HT and FMRFamide on internal Ca2+ concentration ([Ca2+]i). 5-HT caused a 50% increase in the transient rise in [Ca2+]i in response to action potentials, whereas FMRFamide decreased the [Ca2+]i transient by 40%. Neither transmitter altered the resting [Ca2+]i, the time course of recovery of the [Ca2+]i transient, or the [Ca2+]i transients produced by intracellular injection of CaCl2 or inositol 1,4,5-trisphosphate. We conclude that the effects of the transmitters on the action potential-induced [Ca2+]i transient are due to changes in Ca2+ influx and not in intracellular Ca2+ homeostasis.

Autoimmune hemolytic anemia and carcinoma: an unusual association.

Four patients with Coombs'-positive hemolytic anemia associated with carcinoma are presented and compared to 12 previously described patients. These patients commonly seek medical attention for symptoms of anemia rather than for complaints due to the tumor mass. The physician should particularly evaluate for an underlying carcinoma when a patient over the age of 60 years presents with autoimmune hemolytic anemia. Autoimmune hemolytic disease has been demonstrated in patients with a wide variety of tumors, including squamous cell carcinomas, adenocarcinomas, hypernephromas, oat cell carcinomas and a seminoma. Corticosteroid treatment is less effective in autoimmune hemolytic disease associated with carcinoma than in idiopathic autoimmune hemolysis. Tumor extirpation in patients with localized neoplastic disease may abolish the autoimmune hemolytic anemia. Control of the carcinoma through irradiation and chemotherapy together with corticosteroid therapy and/or splenectomy lessened the anemia in some patients. The positive Coombs' test may revert to negative with tumor excision or control. Subsequently, the positivity of the Coombs' reaction may provide a clue to recurrent neoplastic activity. The pathogenic mechanism underlying the association between carcinoma and autoimmune hemolytic disease is poorly understood.

Bacterial challenge study of a porous carbon percutaneous implant.

Numerous percutaneous devices for power transmission and control to electrically powered, intracorporeal blood pumps have been used for periods ranging from 12 months to 4 yrs; however, consistent and reliable performance has not been achieved, due most frequently to the development of infection and sinus tracts at the percutaneous lead exit site. The present study showed that percutaneous devices fabricated from porous vitreous carbon can function satisfactorily in vivo over extended periods. The implant sites successfully resisted infection by normal flora bacteria for as long as 48 months, although superficial surface colonization and infection did occur after deliberate application of pathogens.

Dimethyl sulfoxide alteration of collagen.

In vitro incubation of human scar in our laboratory with 99% DMSO demonstrated, by electron microscopy, the disruption of the collagen fibers. This may prove to be a useful preparatory step for selective enzymatic assault upon exuberant or undesirable scar tissue in the clinical setting. Further study of this concept is planned.

Use of Aplysia neurons for the study of cellular alterations and the resealing of transected axons in vitro.

The present report describes the experimental advantages offered by the combined use of Aplysia neurons and contemporary techniques to analyze the cellular events associated with nerve injury in the form of axotomy. The experiments were performed by transecting, under visual control, the main axon of identified Aplysia neurons in primary culture while monitoring several related parameters. We found that in cultured Aplysia neurons axotomy leads to the elevation of the [Ca2+]i in both the proximal and distal axonal segments from a resting level of 100 nM up to the millimolar range for a duration of 3-5 min. This increase in [Ca2+]i led to identical alterations in the cytoarchitecture of the proximal and distal segments. The formation of a membrane seal over the transected ends by their constriction and the subsequent fusion of the membrane is a [Ca2+]i-dependent process and is triggered by the elevation of [Ca2+]i to the microM level. Seal formation was followed by down-regulation of the [Ca2+]i to control levels. Following the formation of the membrane seal an increase in membrane retrieval was observed. We hypothesize that the retrieved membrane serves as an immediately available membrane reservoir for growth cone extension.

Functional elimination of afferent pathways and decreased safety factor during postembryonic development of cockroach giant interneurons.

The giant interneurons (GIN) from the cockroach CNS undergo two major physiological changes during the postembryonic developmental period: (A) a marked decrease in the number of afferent pathways innervating the GIN at the metathoracic ganglion (Ts); and (B) a gradual decrease in the safety factor for impulse propagation along the intraganglionic segment in T3. In 100% of the experiments (n greater than 100) performed on GIN from early developmental stages, spontaneous postsynaptic potentials (SPSPs) were recorded; in adults, on the other hand. SPSPs have been recorded in only 34% of the experiments (n = 74). Evoked synaptic potentials can be elicited in nymphal stages by stimulation of 8 nerves of T3, the contralateral connectives, ipsi- and contralateral nerve roots 2, 3, 5, and by stimulation of adjacent GINs. In adult, PSPs can be evoked by stimulation of adjacent GINs, and contralateral thoracic connectives, but not from nerves 2, 3 and 5. The functional disappearance of synaptic inputs to the GINs does not reflect a general phenomenon of reduction in synaptic transmission efficacy. In previous studies it was demonstrated that high frequency stimulation of adult GIN leads to blockage of impulse propagation in T3. In nymphal stages, the safety factor for propagation of impulses along T3 is higher. The reduction in safety factor appears gradually during the postembryonic developmental period. From analysis of the mechanisms underlying the elimination of functional afferent pathways and the appearance of low safety factor (see consecutive paper by Yarom and Spira) it is concluded that the functional elimination of afferents is a consequence of decreased transmission efficacy, while the appearance of low safety regions for impulse propagation is a consequence of morphological changes of the GIN segment within ganglion T3.

Morphological and electrophysiological properties of giant interneurons during the postembryonic development of the cockroach CNS.

The giant interneurons (GIN) of the central nervous system of the cockroach undergo two major physiological changes during the postembryonic development period: (A) a gradual decrease in the safety factor for action potential propagation across the GIN in the metathoracic ganglion (T3); and (B) a marked decrease in the number of afferent pathways innervating the GIN in T3 (Spira and Yarom). Analysis of the morphological structure of the GINs, by intracellular injection of cobalt ions and by cross-sections prepared for light and electron microscope, reveals that despite the extensive growth of the GINs during the postembryonic developmental period, the main structural outline of the fibers is not altered. In adult preparations, however, the GIN diameter narrows 25-26% in ganglion T3, while in early nymphal stages the reduction is only 8-10%. The difference in the extent of narrowing of the fibers in adult and nymphal stages is the major factor that accounts for the development of a low safety factor region for impulse propagation across T3. Analysis of the passive membrane properties of the GIN reveals that the electrotonic length of the GIN segment in T3 is identical in adult and nymphal stages. It is concluded that the functional disappearance of afferents innervating the GINs in T3 is a consequence of decreased transmission efficacy along the afferent pathways.

Two distinct propagating regenerative potentials in a single ethanol-treated axon.

Superfusion of the cockroach (Periplaneta americana) giant axon by ethanol (0.5-2%) produces conditions which allow the generation and active propagation of two kinds of regenerative potentials. The classical action potential with a threshold at about 30 mV above resting potential, an amplitude of about 105 mV, a duration of 1-2 ms, and a conduction velocity of 3-6 m/s. A smaller depolarizing potential (SDP) with a threshold of 5-15 mV above resting level, an amplitude of 10-30 mV, a duration of several hundred ms and a conduction velocity of 0.1-0.6 m/s. The SDP is associated with a small increase in conductance (10-15%), and is abolished by tetrodotoxin (10(-6) M) or by removing extracellular sodium. The amplitude of the SDP slightly increases when the extracellular Ca2+ concentration is elevated and is reduced at low (Ca2+)o concentration; however, it is not blocked in a solution containing high Mg2+ (19 mM), low Ca2+ (1 mM) concentrations, indicating that inward Ca2+ current is not required for the generation of SDP.

Penicillin decreases chloride conductance in crustacean muscle: a model for the epileptic neuron.

The effects of penicillin were studied on the neuromuscular preparation of the ghost crab, Ocypoda cursor. Penicillin in doses lower than 2 mM reduced both the amplitude of inhibitory junction potentials and conductance increases induced by external application of GABA. The nature of the latter effect appears to be 2-fold, a weaker competitive inhibition and a more powerful non-competitive effech which may be ionophore blockade. Penicillin in concentrations above 2 mM diminished resting conductance, especially that of chloride. The action of penicillin is, in general, to decrease chloride conductance in this preparation. The crustacean neuromuscular preparation may provide a useful analogue for understanding penicillin evoked epilepsy. The reduced chloride conductance could explain decreased inhibition, increased excitation and depolarization shifts in cortical neurons.

Comparison of ultrastructural changes in proximal and distal segments of transected giant fibers of the cockroach Periplaneta americana.

When the giant axons of the cockroach Periplaneta americana are transected the proximal segment (the part connected to the soma) regenerates by tip sprouting and the distal segment degenerates. The initial ultrastructural response (24-48 h post-transection) occurring in the cut ends of the proximal and distal segments are similar. This response includes the disappearance of neurotubules; appearance of amorphous material in the axoplasm and a gradual accumulation of large numbers of small mitochondria, vesicles of various sizes and smooth endoplasmic reticulum. The axolemma in the region of organelle accumulation invaginates and glial processes are present in the invagination. The similarity of the changes that occur in the cut ends of the proximal and distal segments indicates that the primary reaction to axotomy is of a local nature and does not depend on the soma. Two to four days after transection, the cut end of the distal axonal segment reveals signs of degeneration. These include the appearance of swollen mitochondria, lysosomes, myelinated bodies and shrinking of the axon. In addition there is a massive proliferation of glial processes around the degenerating axons. Sprouting from the tip of the proximal segment starts 5--7 days post axotomy. Sprouts were identified as profiles containing few neurotubules, many vesicles and abundant smooth endoplasmic reticulum. 'Growth cone-like' structures were identified. The ultrastructural reorganization of the cut end of the proximal segment is discussed in relation to changes in membrane properties of the regenerating tip, as previously described by us.