Epidural catheter-induced paresthesia accompanied by changes in skin color and temperature in an obstetric patient.

Placement of epidural catheters for labor analgesia is a common procedure that has become more popular in recent years. However, this procedure can often cause paresthesia, which is typically characterized as a transient and intense burning pain radiating to the hip or leg. In this case report, we describe a patient who had persistent paresthesia in her right foot caused by an indwelling epidural catheter, which was successfully relieved following a partial withdrawal of the epidural catheter. More interestingly, we also observed dramatic changes in skin color and temperature (cold and pale) on her right foot that was well correlated both in time and location with the epidural-induced paresthesia. This cold and pale skin on the right foot represents a localized sympathetic discharge associated with the epidural-induced paresthesia, a phenomenon that has not previously been described. Based on the location of the paresthesia and the pathway of the sympathetic nerve fibers, it is unlikely that this localized sympathetic discharge was due to a direct irritation of the preganglionic sympathetic fibers in the spinal nerve roots by the epidural catheter and thus, a spinal reflex was probably involved. This phenomenon provided us with additional clinical evidence of nerve root irritation, which prompted us to act quickly, and resulted in a favorable outcome.

Evidence that a decrease in opioid tone on proestrus changes the episodic pattern of luteinizing hormone (LH) secretion: implications in the preovulatory LH hypersecretion.

We have studied the LH secretion pattern evoked by diminution in the opioid tone produced by iv naloxone (NAL) infusion between 1100-1400 h on proestrus, the LH secretion pattern occurring spontaneously between 1430-1730 h on proestrus and the LH secretion pattern produced by exogenous LHRH administered either as a 10 ng/pulse at 20-, 30-, or 60-min intervals or infused continuously at a rate of 30 ng/h between 1200-1700 h in rats given pentobarbital at 1100 h on proestrus. Infusion of 0.5 ng NAL/h raised plasma NAL levels to 200-300 ng/ml and augmented LH secretion, as evident by increments in pulse amplitude and frequency discharge to one every 37.5 min from an average of one every 75 min in saline-infused control rats. A 4-fold increase in circulating NAL levels, produced by 2 mg/h NAL infusion, further augmented the frequency of LH episodes to 30-33 min and induced a surge-like LH secretion pattern which resembled that seen on the afternoon of proestrus. Further analysis of the secretory pattern of the preovulatory LH surge (n = 7) showed LH pulses of increased amplitude during the basal phase (n = 4), ascending phase (n = 2), and plateau and descending phases (n = 3); in two rats the LH rise was steep, and no LH pulses were identified. A LHRH pulse (10 ng/pulse) delivered at 20- or 30-min intervals or continuous infusion of LHRH at a rate of 30 ng/h produced LH surges, with peak levels reaching the range seen on the afternoon of proestrus. Further, despite the fact that 10 ng LHRH/pulse at 20-min intervals reproduced a proestrous-type LH surge, only 40% of the LHRH pulses were followed by identifiable LH pulses. Surprisingly, despite the observations that NAL evoked robust LH episodes, the basal pattern of FSH secretion in these rats was not altered. These findings show that a decrease in opioid tone on proestrus accelerates episodic LH discharge to the range that occurs after gonadectomy. A quantitative relationship between the degree of restraint on the opioid tone imposed by NAL and the magnitude of the LH response can be demonstrated. The evidence suggests that the preovulatory LH surge may occur in an episodic fashion and that it can be reproduced by LHRH delivered at a frequency rate of LH pulses seen in ovariectomized rats.(ABSTRACT TRUNCATED AT 400 WORDS)

Patterns of variation in progestin in pregnant sheep.

Patterns of variation in progestin concentrations were studied in pregnant sheep during the last half of gestation. In three sets of experiments, blood was drawn daily or every 4 h for 24 h or every 10 min for 8 h. Peripheral arterial concentration of progestin was examined for 'peaks' using the Pulsar program which identified peaks in daily samples and in samples collected every 10 min, though less often than in daily samples. Ovariectomy did not affect the frequency or character of the peaks. The data suggest that large variations in progestin concentrations occur during the last half of pregnancy. They are superimposed on a gradual increase in average concentration and last for 2 to 3 days.

Cx36 and the function of endocrine pancreas.

The secretory, duct, connective and vascular cells of pancreas are connected by gap junctions, made of different connexins. The insulin-producing beta-cells, which form the bulk of endocrine pancreatic islets, express predominantly Cx36. To assess the function of this connexin, we have first studied its expression in rats, during sequential changes of pancreatic function which were induced by the implantation of a secreting insulinoma. We observed that changes in beta-cell function were paralleled by changes in Cx36 expression. We have also begun to investigate mutant mice lacking Cx36. The absence of this protein did not affect the development and differentiation of beta-cells but appeared to alter their secretion. We have studied this effect in MIN6 cells which spontaneously express Cx36. After stable transfection of a construct that markedly reduced the expression of this connexin, we observed that MIN6 cells were no more able to secrete insulin, in contrast to wild type controls, and differentially displayed a series of still unknown genes. The data provide evidence that Cx36-dependent signaling contributes to regulate the function of native and tumoral insulin-producing cells.

Maturational and anesthetic effects on apneic thresholds in lambs.

Periods of apnea are relatively common in newborns but rare in older infants. Postnatal changes in the response of the central neural respiratory circuits to afferent inputs may have a role in the age-related incidence of apnea. Therefore we determined the central neural apneic threshold to CO2 and superior laryngeal nerve (SLN) stimulation in halothane-anesthetized newborn (4- to 7-day-old) and older (45- to 56-day-old) lambs. The animals were vagotomized, paralyzed, and mechanically ventilated with hyperoxic gas. Phrenic nerve activity served as a monitor of central respiratory output. The CO2 and SLN apneic thresholds were defined as the arterial PCO2 when phrenic activity began after hyperventilation, and the quantity of current applied to the SLN that abolished phrenic activity, respectively. At equivalent concentrations of halothane, newborn lambs had higher CO2 apneic thresholds (P less than 0.05) and lower SLN apneic thresholds (P less than 0.05) than did older lambs. Increasing concentrations of halothane decreased (P less than 0.05) the SLN apneic threshold and increased (P less than 0.05) the CO2 apneic threshold. Equal incremental changes in halothane concentration induced similar changes in the apneic thresholds of both ages of lambs. The data suggest that with maturation, the central neural respiratory circuits become more responsive to CO2 and less responsive to SLN afferents. Halothane alters central neural responsiveness to these inputs in both ages similarly.

Beta-cell crosstalk: a further dimension in the stimulus-secretion coupling of glucose-induced insulin release.

Pancreatic beta-cells are connected by gap junction channels made of a connexin protein, referred to as Cx36. Through these channels, beta-cells are coupled to each other, i.e. exchange cytoplasmic ions and small metabolites. Previous experiments have indicated that these exchanges are important for coordinating the function of individual cells within pancreatic islets, particularly with regard to glucose-induced insulin secretion. Advances in molecular biology, genetics and mouse transgenic approaches allow now for a direct experimental testing of this mechanism in vitro as well as in vivo. Recent experiments in rodent and culture models suggest that connexin-dependent cell-to-cell crosstalk is a significant player in the multifactorial regulation of insulin secretion and, possibly, of other beta-cell functions, such as growth. Elucidating the still obscure mechanism whereby connexin signalling exerts this influence will provide insights on the contribution of direct cell-to-cell interactions in the physiological regulation of beta-cell life. The presence of Cx36 within human pancreatic islets, raises the further challenge to determine whether a dysfunction of connexin signaling may contribute to the pathophysiology of beta-cell dysfunctions in type I and/or type II diabetes. Efforts to understand the functions of beta-cell connexins are also a prerequisite for the engineering of surrogate cells and their proper tridimensional packaging, which are instrumental for the future implementation of a replacement cell therapy in diabetic patients.

Partitioning the respiratory effects of airway citric acid and normal saline in lambs.

Aspiration is common in the intubated human neonate. Thus, the ventilatory and blood gas responses to citric acid and saline instillation into different airway sites were studied in ten awake, unanesthetised lambs, breathing spontaneously via a tracheostomy tube. With a system of balloons, 1 ml of saline or citric acid was placed selectively into the midtrachea, the laryngeal area, or the lower trachea (lower tr). Changes in minute ventilation (VE), after a 30 sec baseline period, were measured 30 sec and 1 and 2 min after the challenge. Arterial blood gas changes were measured at 30 sec and 2 min. Major increases in VE were seen only when saline or citric acid was instilled into the lower tr, the citric acid responses exceeding saline ones. The arterial oxygen tension (PaO2) fell after lower tr saline, whereas the arterial CO2 tension (PaCO2) fell with midtracheal saline instillation. A rise in pH and a fall in PaCO2 accompanied citric acid given into the lower tr. An initial rise in PaO2 after citric acid into the lower tr was followed by a return to baseline despite hyperventilation. The ventilatory and blood gas changes with saline and citric acid depend on the site of airway instillation.

Metkephamid-induced Flehmen in lambs.

When metkephamid, a systemically active analog of methionine enkephalin, was administered intracisternally to male or female prepubescent lambs as early as the first week of life, we observed a behavioral pattern akin to Flehmen, which is a well-characterized grimace displayed by mature ungulates during mating. This metkephamid-induced Flehmen was preceded by transient bradycardia and apnea followed by somnolence for approximately 1 hour, during which Flehmen was observed intermittently. Pretreatment with the specific opiate antagonist, naloxone, blocked this behavioral response. These observations indicate that endogenous opioid peptides may be involved in Flehmen.

Burnout and stress among employees at a state institution for mentally retarded persons.

The effects of burnout of 192 employees of a state institution were examined to determine whether these problems were different from conditions resulting from stress. Each subject completed a packet including the Maslach Burnout Inventory and Ivancevich's Job Stress Scale. For all groups, high burnout emerged in the form of low personal accomplishment, with moderate degrees of burnout measured by the Burnout Inventory subscales Emotional Exhaustion and Depersonalization. One of the stress variables (underutilization) correlated significantly with one Burnout Inventory subscale (Emotional Exhaustion). Results generally indicated that stress and burnout were separate constructs that can be best thought of as distinct entities.

Conceptus development, uterine response, blood gases and endocrine function of gilts exposed to increased ambient temperature during early pregnancy.

Fifteen crossbred gilts were used to determine the influence of heat stress during Days 8 to 16 after onset of estrus on the development of conceptuses and uterine and endocrine functions. Ten gilts were bred 12 and 24 h after the onset of estrus (Day 0), and five gilts were nonbred controls. On Day 5, catheters were inserted into the uterine-ovarian vein (UV), saphenous artery (SA) and saphenous vein (SV) of each gilt. An electromagnetic blood flow transducer was implanted around the main uterine artery. Pregnant (n=5) and nonbred (n=5) control gilts were exposed to 21 +/- 1 degrees C, and pregnant heat-stressed gilts (n=5) were exposed to 37 +/- 1 degrees C for 12 h and 32 +/- 1 degrees C for 12 h daily during Days 8 through 16 after estrus. Treatment did not influence the partial pressure of oxygen (PO(2)) and of carbon dioxide (PCO(2)) in the UV, SA and SV blood. Uterine blood flow was not altered by heat stress. On Day 16, total wet weight of conceptuses was reduced in the gilts that were heat-stressed compared with conceptuses from control gilts. Incorporation of (3)H-leucine into macromolecules in vitro by conceptuses from the heat-stressed gilts was reduced compared with control gilts. Concentrations of 15-keto-13, 14-dihydro prostaglandin F(2alpha) (PGFM) in peripheral blood were greater than 1 ng/ml between Days 13 to 16 after estrus in 20% of the pregnant control gilts, 60% of the heat-stressed pregnant gilts, and 100% of the nonbred gilts. Concentrations of estradiol in the SA were affected by treatment. These results indicate that heat stress of gilts between Days 8 to 16 after estrus reduced the amount of conceptus tissue and altered concentrations of estradiol in the peripheral circulation, but uterine blood flow and PO(2) and PCO(2) in blood were not affected.

Technical note: subjective enumeration of episodic events (spikes) in animal physiology experiments.

Blood samples of nine sheep were taken over time and analyzed for estrone, estradiol, and progesterone. Results were plotted for each sheep, and graphs were evaluated by 26 evaluators with various previous experience. Sheep were sampled for different time periods. Repeatabilities for the number of spikes of estrone, estradiol, and progesterone recorded for sheep were variable, ranging from .019 to .547. Repeatabilities for evaluators ranged from .033 to .427, but these values decreased to < .001 to .030 when adjusted by covariance for the number of spikes possible. Results indicated that either an objective procedure for counting spikes should be used in comparable research or that evaluators should be trained in visual counting procedures to improve their repeatability.

Ovarian function during the estrous cycle of the cow: ovarian blood flow and progesterone release rate.

To study the function of the corpus luteum (CL) through its major secretory product, progesterone (P4), catheters were inserted into the carotid artery (via the facial artery) and the ovarian vein (n = 12), and electromagnetic flow transducers were placed around the ovarian artery in cycling Angus and Hereford cows (n = 6). Blood samples were taken four times daily (at 0600, 1200, 1800 and 2400 h) and ovarian blood flow (OBF) was monitored for 60 min immediately after each blood sampling. After chromatography, P4 was measured by radioimmunoassay. The P4 concentrations in the ovarian vein (OP4) were correlated with day of the estrous cycle (r = .25; P less than .05) and were higher during the morning hours (P less than .05). Arterial progesterone (SP4) was correlated to OP4 (r = .24; P less than .05) and day of the cycle (r = .35; P less than .05). The OBF changed among days (P less than .05). The highest rates were noted during luteal maturation (23 ml/min; SE = .09) and the lowest were noted with the demise of the CL (SP4 less than 1 ng/ml) and approach of estrus (8 ml/min; SE = .07). The OBF was correlated with SP4 (r = .24; P less than .05), although no within-day trends were noted. Exogenous estrone (6 mg) administered via jugular vein decreased OBF within 30 to 45 min, but similar injections of P4 (up to 100 mg) had no effect. Progesterone release (P4R) from the ovary [(OP4 - SP4) x OBF] was higher in the morning hours (P less than .05). The P4 concentration (OP4, SP4) and release (P4R) exhibited wide variations among and within days. The changes in OP4 and P4R were both good indicators of CL development, maturation and regression, as associated with SP4 changes. Oxygen (O2) and carbon dioxide (CO2) concentrations monitored in the carotid artery and ovarian vein indicated that the ovary with the CL was not limited in O2 availability or CO2 removal during periods of low blood flow or high secretion of P4.

Method for obtaining ovine uterine secretions from unilaterally pregnant ewes.

Development of the ovine conceptus was confined to the uterine horn ipsilateral to the corpus luteum (CL) by placing a ligature around that uterine horn at a point near the uterine body on day 5 of pregnancy. On day 140 of gestation, seven of 10 ewes were still pregnant and from 21 to 815 ml of uterine fluid (488 +/- 94 ml, X +/- SEM) were collected from the nongravid uterine horn. Total recoverable protein (X +/- SEM) was 13.4 +/- 3.4 grams. Polyacrylamide gel electrophoresis of the reduced proteins in presence of sodium dodecyl sulfate indicated that protein composition of uterine fluid was distinct from that of colostrum, serum, amniotic fluid, and allantoic fluid, and revealed the presence of two major polypeptides with molecular weights of about 57,000 and 58,500, respectively, plus numerous other minor components. Gel filtration on columns of Sephadex G-200 and Sepharose CL-6B suggested that these polypeptides formed a series of aggregates of high molecular weight when kept under nonreducing conditions. Glucose (.18 +/- .03 mg/ml), but not fructose, was present in uterine fluid. In addition, high levels of prostaglandin F (451.4 +/- 83.3 ng/ml) were present.

Medical science and social values.

Social Values, no less than medical science, have shaped the medical management of the pain of childbirth. Nineteenth century feminists fought for greater use of anesthesia in obstetrics at a time when physicians held back for fear of its effects on labor, hemorrhage, rates of infection and the condition of the child. A century later, after physicians became comfortable with the use of anesthesia, a new generation of feminists challenged the use of such drugs, once again citing social considerations. The personalities of colorful and charismatic obstetricians such as James Young Simpson and Grantley Dick-Read played a strong part in the outcome of each confrontation.

John Snow's practice of obstetric anesthesia.

The influence of Queen Victoria on the acceptance of obstetric anesthesia has been overstated, and the role of John Snow has been somewhat overlooked. It was his meticulous, careful approach and his clinical skills that influenced many of his colleagues, Tyler-Smith and Ramsbotham and the Queen's own physicians. The fact that the Queen received anesthesia was a manifestation that the conversion of Snow's colleagues had already taken place. This is not to say that this precipitated a revolution in practice. Medical theory may have changed, but practice did not, and the actual number of women anesthetized for childbirth remained quite low. This, however, was a reflection of economic and logistical problems, too few women were delivered of newborn infants during the care of physicians or in hospitals. Conversely, it is important to recognize that John Snow succeeded in lifting theoretical restrictions on the use of anesthesia.