Immunity against MOPC 104E plasmacytoma: effects of tumor size and time post therapy on in vivo tumor immunity.

BALB/c mice with the plasmacytoma MOPC 104E were cured of palpable tumors (6-15x10(7) cells) with a single injection of cyclophosphamide (10 mg/kg). Animals cured of tumor showed a considerable increase in their ability to reject secondary challenge with graded numbers of viable tumor cells. Mice with palpable subcutaneous tumors were cured therapeutically and rechallenged 22, 44, or 120 days post therapy. The ability of such animals to reject secondary tumor cell challenge was similar in all groups, which implied that in vivo tumor immunity remained relatively constant for at least 4 months post therapy. A second group of animals was treated therapeutically (10 mg cyclophosphamide/kg) 4, 11, or 20 days post tumor cell injection. These therapeutically treated animals were then rechallenged with various numbers of viable tumor cells 30 days post therapy. Mice given cyclophosphamide 4, 11, or 20 days post tumor injection rejected 6, 60, or 400 times as many tumor cells, respectively, as did control animals. These results implied that, over the range of tumor sizes investigated, exposure to greater amounts of tumor antigen resulted in increasing amounts of residual tumor immunity following cure.

Therapy of the murine plasmacytoma MOPC 104E: role of the immune response.

The murine plasmacytoma MOPC 104E was susceptible to cytotoxic therapy in female inbred BALB/c mice. Palpable subcutaneous tumors (0.6--1.2 X 10(8) cells) could be cured with a single administration of cyclophosphamide (5--250 mg/kg) or localized irradiation (800--2,400 R). Clonogenic assay showed that, following minimal curative doses of cyclophosphamide or radiation, 0.5--1.5 X 10(6) tumor cells should remain viable. Control animals succumbed to progressive, invariably lethal tumor growth after they were given sc injections of 2--3 X 10(3) tumor cells. Minimal doses of cyclophosphamide, which were curative in control tumor-bearing animals, were ineffective in treating tumor-bearing animals immunosuppressed by 450 R whole-body irradiation. Subsequent experiments measured the ability of animals cured of the murine plasmacytoma to reject secondary challenge with the same tumor. These experiments demonstrated and partially quantitated the substantial role of the immune response in effecting tumor cure following radiotherapy or chemotherapy.

Effects of vasopressin antiserum on the response of adrenocorticotropin and cortisol to hemorrhage.

To determine if arginine vasopressin (AVP) is involved in the response of ACTH and cortisol (F) to hemorrhage, we examined the effect of injections of AVP-antiserum into the third ventricle in chronically prepared awake cats. Cats were trained to remain unrestrained in a cardboard box. Cats were prepared under halothane and nitrous oxide with aseptic technique. Two to 3 days later, experiments began. Antiserum (5 microliters) to AVP or to oxytocin (OXY) as a control was given 26 min before hemorrhage conducted over 3 min. Thirty minutes after hemorrhage, reinfusion was conducted over 3 min. Each cat received each antiserum in randomized sequence 2-3 days apart. Plasma ACTH and F were measured by RIA. Data were analyzed statistically by analysis of variance. In 12 experiments in 6 cats, ACTH and F increased significantly with 10 ml/kg hemorrhage (P less than 0.01) and to the same extent (P greater than 0.1) after either antiserum. In 20 additional experiments in 10 cats, a submaximal dose of dexamethasone was administered sc 2-3 h before hemorrhage of 15 or 17.5 ml/kg. Under this circumstance, ACTH increased significantly (P less than 0.05) after anti-OXY, but not after anti-AVP (P greater than 0.2) so that during hemorrhage the values of ACTH differed significantly (P less than 0.025). F increased significantly more after anti-OXY than after anti-AVP (P less than 0.025). Changes in arterial pressure, heart rate, and plasma glucose with or without pretreatment with dexamethasone did not differ between groups. Changes in F and ACTH in cats receiving sham injections did not differ from those after anti-OXY. These findings suggest that normally a corticotropin-releasing factor (CRF) or factors act independently of AVP to mediate the response to hemorrhage. However, in the presence of steroid feedback by dexamethasone, the release or action of this CRF(s) is suppressed so that AVP is necessary for a full response. As has been proposed previously by others, AVP could potentiate the action of other CRFs, stimulate their release, or act as a CRF.

Response of plasma adrenocorticotropin to injections of L-glutamate or norepinephrine in the dorsal rostral pons of cats.

Previously, electrical stimulation of several nuclei in the dorsal rostral pons of the cat was shown to modulate the release of ACTH. However, the stimulation may have activated fibers of passage. To determine if there are specific groups of neurons within the pons that modulate plasma ACTH when stimulated with glutamate, 30 cats were prepared acutely under chloralose anesthesia. Microinjections of several agents were made at each of 2 sites in the pons of each cat. ACTH was measured by RIA. Injections of 150 mM L-glutamate (100 nl/min.2 min) elicited increases in arterial pressure that were related to the loci of injection. The responses did not decrease significantly when the rate and volume of the injection were reduced by half. Eight sites in a lateral area that extended rostrally from the parabracheal nucleus elicited a significant pressor response that was greater in duration and magnitude than a second significant pressor response that was obtained from 18 sites in a medial area that included the rostral locus coeruleus. Pressor responses did not occur when 0.1 mM norepinephrine or vehicle was substituted for L-glutamate in any area. The larger, but not the smaller, dose of L-glutamate elicited changes in plasma ACTH that were related to the loci of injection. Eight sites in a caudal area that included the ventral locus coeruleus and was within the medial pressor area elicited a significant increase in ACTH. Seven sites in an area rostral to the ventral locus coeruleus that included the rostromedial locus subcoeruleus elicited a significant decrease in plasma ACTH. ACTH responses were not observed when 0.1 mM norepinephrine or vehicle was substituted for L-glutamate in any area. In conclusion, the ventral locus coeruleus and the rostrally adjacent locus subcoeruleus contain neurons with receptors for L-glutamate that can modulate plasma ACTH and arterial pressure independently of a second pathway that includes the parabracheal region and influences arterial pressure. Because the neurons in the coeruleus are known to respond to hemodynamic input, they may participate in the hemodynamic control of ACTH release.

Alpha-adrenergic input in the locus coeruleus modulates plasma adrenocorticotropin in cats.

Previous evidence suggested that noradrenergic activity in the vicinity of the ventrorostral locus coeruleus (LC) increased in response to hemorrhage. To investigate the possible role of this response in the control of ACTH release, microinjections (100 nl/min for 2 min) of several agents were made at 59 sites in 35 cats anesthetized with chloralose. Injections were as follows: vehicle (all sites); 150 mM L-glutamate (GLU; 51 sites); an alpha 2-agonist, 1 mM clonidine (19 sites); an alpha 2-antagonist, 1 mM yohimbine (32 sites); an alpha 1-agonist, 1 mM phenylephrine (PE; 42 sites); and an alpha 1-antagonist, 0.05 mM prazosin (20 sites). Plasma ACTH was measured by RIA. Responses were tested statistically by repeated measures analysis of variance. GLU at 12 sites in the region of the ventrorostral LC facilitated plasma ACTH (P less than 0.01), whereas GLU at 6 sites in the caudal LC inhibited ACTH (P less than 0.05). Clonidine at 9 sites in an area that included the ventrorostral LC inhibited ACTH (P less than 0.05), and yohimbine at 7 sites within this latter area facilitated ACTH (P less than 0.01). PE within the ventrorostral LC had no effect on ACTH. However, PE at 10 sites within the caudal LC and along the ventromedial border of the ventrorostral LC facilitated ACTH. The responses for all of these areas to the respective agents differed from those to vehicle, whereas responses from other areas to the former agents or from all areas to prazosin did not. An increase in noradrenergic turnover in the LC may provide inhibitory alpha 2 modulation to the neurons in the LC that are activated by hemorrhage. This modulation and possible alpha 1 input in areas adjacent to the ventrorostral LC may influence the hemodynamic control of ACTH release.

Organization of the lateral hypothalamus for control of adrenocorticotropin release in the cat.

Regions in the ventral midbrain that project to the lateral hypothalamus have been implicated in the control of ACTH release. To define further those areas in the lateral hypothalamus through which afferent signals might pass, we electrically stimulated 188 sites in the lateral hypothalamus of 20 cats anesthetized with chloralose-urethane. Stimulations were monophasic pulses of DC (200 microA; 0.2 msec; 100 Hz; 20 sec). Venous samples were drawn over 30 sec 0.5 min before and 1.5 min after stimulation. Equal volumes of warmed isoncotic dextran were infused during sampling to prevent hypovolemia. ACTH was assayed by RIA. Areas were defined in which stimulation led to increased, decreased,, or unchanged ACTH. Mean changes in ACTH were tested by analysis of variance. The present data indicate that the ACTH-active areas defined previously in the midbrain may join the medial forebrain bundle in the subthalamic area and nucleus to traverse the lateral hypothalamus. At the level of the mammillary bodies, a facilitatory area occupied the ventral portion of the medial forebrain bundle. This area extended rostrally and medially to join the medial aspect of the medial forebrain bundle. Continuity with the mediobasal hypothalamus was seen only anteriorly in the area of the supraoptic decussations. An inhibitory area occupied the dorsal extent of the medial forebrain bundle at the level of the mammillary bodies. It extended rostrally and laterally around the caudal pole of the supraoptic nucleus and then medially at the level of the optic chiasm. There appear to be no other medial projections of the lateral lying ACTH-active areas to the mediobasal hypothalamus. The lateral hypothalamus may serve as a site of passage and/or of processing of information that ascends from the midbrain and descends from the limbic system.

Organization of the medial hypothalamus for control of adrenocorticotropin in the cat.

To examine the role and interrelations of areas of the medial hypothalamus in the control of release of ACTH, we stimulated electrically (20-sec train, 200-microamperemeter amplitude at 100 Hz) 695 sites in the hypothalamus of 91 cats anesthetized with chloralose-urethane. Changes in ACTH were measured by RIA. Responses of arterial pressure could not account for changes of release of ACTH. Several ACTH-active areas were defined. The anatomical relations of these areas with known nuclei and pathways then were considered. Two ACTH facilitatory areas and one ACTH inhibitory area were identified in the lateral aspect of the medial hypothalamus. The dorsal facilitatory area appears to be an extension of the lateral division of the dorsolongitudinal fasciculus and to extend medially to join the Fields of Forel, the ventral tegmental area of Tsai, and the parvocellular, paraventricular, and periventricular nuclei. The ACTH inhibitory area appears to be an extension of portions of the central tegmental tract and to extend medially to the posterior hypothalamic area and the dorsal hypothalamic area and ventrally toward the basal hypothalamus. The ventral ACTH facilitatory area appears to be coincident with the medial forebrain bundle and to extend anteroventrally and medially through the supraoptic decussation to the suprachiasmatic, ventromedial, dorsomedial, periventricular, infundibular, and premammillary nuclei. Stimulation of the median eminence led to increased release of ACTH. The results suggest that ascending pathways from the lower brainstem mediating control of ACTH project to discrete areas of the hypothalamus and then converge on the medial basal hypothalamus.

Vasopressin-dependent and -independent control of the release of adrenocorticotropin.

We tested the possibility that vasopressin mediates the responses of adrenocorticotropin (ACTH) to electrical stimulation of various areas of the hypothalamus. Thirty-three cats were anesthetized with chloralose-urethane, immobilized with gallamine, and respired artificially. Plasma ACTH was measured by RIA. Intraventricular administration of antiserum to vasopressin blocked the release of ACTH induced by electrical stimulation of the paraventricular nucleus (PVN), suggesting a role for the vasopressinergic projection from PVN to the external zone of the median eminence. In contrast, the release of ACTH induced by stimulation of areas ventral to PVN was unaffected by the antiserum. Thus, there is at least one corticotropin releasing factor released from nuclei other than PVN that is distinct from vasopressin.

Control of release of adrenocorticotropin and vasopressin by the supraoptic and paraventricular nuclei.

To determine the relative roles of the hypothalamic supraoptic (SON) and paraventricular (PVN) nuclei in the control of the release of vasopressin and of ACTH, we have examined the hormonal responses to electrical stimulation (200 microA, 0.2 msec, 100 Hz, 20 sec) of these regions. Cats were anesthetized with chloralose-urethane. Blood samples were taken 30 sec before stimulation and 1.5 min poststimulation. ACTH and vasopressin were measured by RIA. Electrical stimulation of the caudal pole of the SON increased vasopressin in plasma (1.82 +/- 0.41 microU/ml, n = 17, P less than 0.01) and decreased ACTH (-26 +/- 4 pg/ml, n = 13, P less than 0.01). In contrast, stimulation of the PVN increased vasopressin (2.01 +/- 0.60 microU/ml, n = 7, P less than 0.001) and increased ACTH (107 +/- 20 pg/ml, n = 32, P less than 0.01). Previous work has shown that vasopressinergic neurons of PVN, but not of SON, project to the zona externa of the median eminence. Other have suggested that the retrograde flow of blood from the neural lobe to the median eminence and thence to the anterior lobe would allow vasopressin to influence the release of ACTH. The present results indicate that both SON and PVN facilitate the release of vasopressin. However, PVN facilitates, but SON inhibits the release of ACTH. These findings suggest that the projection from PVN to the zona externa of the median eminence mediates the release of ACTH and that retrograde flow from the neural lobe is not important in the control of ACTH release during modest and transient increases in the release of vasopressin.

Post-surgical recovery and time-of-day mask potentiated responses of ACTH to repeated moderate hemorrhage in conscious rats.

We determined how changes in the responsiveness of the hypothalamo-pituitary-adrenal (HPA) system that accompany experimentation affect facilitation of HPA responses to hemorrhage. Hemorrhage (10 ml/kg over 3 min) was performed in conscious, chronically prepared rats. Blood was sampled over 1 h followed by reinfusion of shed blood. Hemorrhage was performed either once or twice separated by 24 h in different groups of animals. To test the effect of the circadian variation in responsiveness, rats were hemorrhaged on days 4 and 5 after surgery either in the morning (AM) or in the afternoon (PM). The response of ACTH to hemorrhage on day 4 was greater in the PM than in the AM (P<0.01). The ACTH response to the second hemorrhage on day 5 was greater than that to hemorrhage on day 4 only in the AM group (P<0.01). Thus, facilitation of ACTH responses by prior hemorrhage was evident only in the AM. To determine the effects of surgical recovery, additional experiments were done in the AM either early (days 3 and 4) or later (days 6 and 7) after surgery. In these experiments, hemorrhage was performed in all rats on days 4 and 7 and either hemorrhage or blood sampling alone was performed on day 3 and 6. ACTH did not increase in rats with sampling and no hemorrhage. ACTH increased more after an initial hemorrhage on day 3 than on day 6 (P<0.01). ACTH response to hemorrhage on day 4 was greater when preceded by hemorrhage vs sampling on day 3 (P<0.01). ACTH response to hemorrhage in rats bled twice did not differ on day 3 and day 4. On day 7, the response of ACTH in rats that had hemorrhage on day 6 was greater than both their own response on day 6 and the response of a control group with sampling on day 6 (P<0.01). These results demonstrate potentiation of ACTH responses to hemorrhage by an earlier similar hemorrhage, but clearly indicate that enhanced sensitivity of the HPA to hemorrhage either by circadian factors or by surgery can mask this effect.

Mosaic trisomy 16 ascertained through amniocentesis: evaluation of 11 new cases.

Trisomy 16, once thought to result uniformly in early pregnancy loss, has been detected in chorionic villus samples (CVS) from on-going pregnancies and was initially ascribed to a second, nonviable pregnancy. Prenatally detected trisomy 16 in CVS and its resolution to disomy has led to the reexamination of the viability of trisomy 16. This study evaluates 11 cases of mosaic trisomy 16 detected through second trimester amniocentesis. In 9 of the 11 cases, amniocenteses were performed in women under the age of 35 because of abnormal levels of maternal serum alpha-fetoprotein (MSAFP) or maternal serum human chorionic gonadotropin (MShCG). The other two amniocenteses were performed for advanced maternal age. Five of the 11 pregnancies resulted in liveborn infants, and six pregnancies were electively terminated. The liveborn infants all had some combination of intrauterine growth retardation (IUGR), congenital heart defects (CHD), or minor anomalies. Two of them died neonatally because of complications of severe congenital heart defects. The three surviving children have variable growth retardation, developmental delay, congenital anomalies, and/or minor anomalies. In the terminated pregnancies, the four fetuses evaluated by ultrasound or autopsy demonstrated various congenital anomalies and/or IUGR. Cytogenetic and fluorescent in situ hybridization studies identified true mosaicism in 5 of 10 cases examined, although the abnormal cell line was never seen in more than 1% of cultured lymphocytes. Placental mosaicism was seen in all placentas examined and was associated with IUGR in four of seven cases. Maternal uniparental disomy was identified in three cases. Mosaic trisomy 16 detected through amniocentesis is not a benign finding but associated with a high risk of abnormal outcome, most commonly IUGR, CHD, developmental delay, and minor anomalies. The various outcomes may reflect the diversity of mechanisms involved in the resolution of this abnormality. As 80% of these patients were ascertained because of the presence of abnormal levels of MSAFP or MShCG, the increased use of maternal serum screening should bring more such cases to clinical attention.

Adrenocorticotropin correlates strongly with endotoxemia after intravenous but not after intraperitoneal inoculations of E. coli.

To determine the influence of the site of infection on circulating endotoxin and hormonal release, male rats were prepared with arterial catheters and with either intravenous (i.v.) or intraperitoneal (i.p.) catheters under pentobarbital. Four days later, they were injected either i.v. or i.p. with Escherichia coli suspended in saline. Plasma was assayed for adrenocorticotropin (ACTH), corticosterone, and endotoxin activity. After approximately 10(9) colony-forming units (CFU) of E. coli, plasma endotoxin in i.v. rats (496 +/- 96 EU/mL) differed from that in i.p. rats (12.6 +/- 3.6 EU/mL, p < .01). However, ACTH and corticosterone increased to the same extent in both groups. After approximately 10(7) CFU, plasma endotoxin in i.v. rats (9.15 +/- 2.09 EU/mL) was greater than in i.p. rats (2.56 +/- .42 EU/mL, p < .05), and ACTH and corticosterone increased more at 1 h in i.v. rats than in i.p. rats (p < .01). Additional rats given approximately 0.3 x 10(9) CFU i.p. had plasma endotoxin that did not differ from values measured after either approximately 10(9) CFU i.p. or approximately 10(7) CFU i.v. However, the ACTH responses in these three groups differed from one another (p < .01). ACTH was more strongly correlated to plasma endotoxin in i.v. rats (r = .915) than in i.p. rats (r = .528, p < .01 for difference from i.v. group). The weak relationship between plasma endotoxin and ACTH after i.p. inoculations suggests that peritoneal infections activate important pathways that are independent of the circulation.

Neural control of ACTH release in response to hemorrhage.

A three dimensional reconstruction of the central neural pathways that appear to mediate release of ACTH in response to hemodynamic change is illustrated in Figure 11. Fibers from receptors in the right atrium and the carotid arteries project to the lateral solitary nucleus and then to the medial and the lateral nucleus intercalatus. A pathway containing projections from these nuclei then converges dominantly in the locus subcoeruleus and locus coeruleus. Multiple pathways then diverge, to travel in part directly to the hypothalamus through dorsal pathways. One pathway inhibits and another facilitates the release of ACTH. Multiple pathways also diverge, to travel in part medially, and then to the hypothalamus through ventral pathways. Again, one pathway inhibits and another facilitates the release of ACTH. The dorsal and ventral inhibitory pathways appear to converge in a region extending from just caudal and ventral to the paraventicular nucleus to the posterior hypothalamic area. Thus, after the coalescences of the various pontine-hypothalamic pathways, three principal pathways remain. These include a posterior inhibitor path, an anterodorsal facilitatory path that terminates in the paraventricular nucleus and that may be mediated through release of vasopressin, and an anteroventral facilitatory path that terminates in the suprachiasmatic and ventromedial nuclei and that is probably mediated through release of corticotropin-releasing hormone. The mode of integration of these pathways has not been defined. The pathways described herein are oligosynaptic: a signal may travel from atrium to hypothalamus over three to seven neurons. The combination of control of input hemodynamic signals and of measurement of ACTH permits quantitation of both sensory and motor events, that inevitably must be embedded in the neuronal pathways described here. The analysis of the input-output relations and their correlation with internal neural events must form the basis of a description of the physiology of the physiology of the system whose central neural anatomy has been defined in part by these studies.

Role of solute in the early restitution of blood volume after hemorrhage.

We examined the putative roles of decreased capillary pressure and increased transcapillary osmolar gradient in mediation of the early restitution of blood volume after hemorrhage by comparing the degree of restitution of plasma volume and protein and comparing changes in capillary pressure and osmolality in awake dogs with those in dogs anesthetized with pentobarbital. Decreases in estimated capillary pressure and increases in plasma osmolality were greater in anesthetized than in awake dogs. However, early restitution of plasma volume and of protein was greater in awake animals. Analysis of the Starling forces indicated that interstitial hydrostatic pressure was greater in awake animals than in anesthetized animals, suggesting that interstitial volume increases more rapidly in awake animals. Selective venous sampling in anesthetized dogs indicated that the splanchnic and renal vascular beds release solute to the circulation following hemorrhage. However, rather than promoting the restitution of blood volume by production of a transcapillary osmolar gradient, the data suggest that the solute is delivered to the peripheral tissues, where it mediates the movement of water from cells to the interstitium more rapidly in awake than in anesthetized dogs. It thus appears that the early metabolic changes after hemorrhage, resulting in increased solute production, are important for the early restitution of blood volume and plasma protein.

Quantifiable polyhydramnios: diagnosis and management.

Little has been written regarding the ultrasonographic quantification of polyhydramnios or its subsequent management. Therefore, we designed this study to define polyhydramnios using the amniotic fluid index of greater than 2 SDs above the mean for late second- to third-trimester pregnancies, or 24 cm or greater. One hundred twelve nondiabetic women referred to Women's Hospital, Los Angeles County/University of Southern California Medical Center with the descriptive diagnosis of polyhydramnios made by experienced ultrasonographers were included in the study. There was poor correlation between these descriptions and fetal outcome. Twenty-six were qualitatively described as having severe, 29 as moderate, and 57 as mild polyhydramnios. Forty-nine of the 112 patients met our definition of significant polyhydramnios by having an amniotic fluid index of 24 cm or more. This particular definition allowed the inclusion of all fetuses with serious structural defects and/or death. Seven patients had an amniotic fluid index less than 24 cm, but with the traditional quantitative definition of one pocket of 8 cm or more; none of these patients had poor fetal outcome. These data appear to suggest that the use of descriptive definitions of polyhydramnios or a single fluid pocket of 8 cm or greater should be discarded in favor of using an amniotic fluid index of 24 cm or more. Once the diagnosis of polyhydramnios is made, the patient should have a detailed sonographic evaluation, be offered cytogenetic studies, and have antepartum surveillance.

The ultrasound triad of fetal hydramnios, abnormal hand posturing, and any other anomaly predicts autosomal trisomy.

Our definition of hydramnios is an amniotic fluid index of 24 cm or greater. We evaluated by ultrasound examination 49 consecutive patients who met this definition of hydramnios. Of these, 22 (44.9%) had anomalies visible by ultrasound. The combination of hydramnios, abnormal hand posturing, and any other anomaly created a constellation of sonographic findings enabling us to predict six specific autosomal trisomies (27.27%): three trisomy 18, two trisomy 21, and one trisomy 13. The 27 fetuses with "idiopathic hydramnios" (no identifiable anomaly or abnormal hand posturing) had normal karyotypes. We recommend that any patient with confirmed hydramnios have a detailed ultrasound examination by an experienced sonographer, with special attention paid to the heart, face, and hands. If no abnormality is seen and the hands are normally postured, expectant management may be appropriate. If the late second- or third-trimester fetus displays abnormal hand posturing with any other abnormality, rapid karyotyping by funipuncture or placental biopsy should be recommended to facilitate appropriate management.

Baroreceptor-mediated compensation for hemodynamic effects of positive end-expiratory pressure.

The roles of the carotid arterial baroreceptor reflex and of vagally mediated mechanisms during positive end-expiratory pressure (PEEP) were determined in pentobarbital-anesthetized dogs with isolated carotid sinuses. Spontaneously breathing dogs were placed on PEEP (5-10 cmH2O) with the carotid sinus pressure set to the systemic arterial pressure (with feedback) or to a constant pressure (no feedback). Right atrial volume was measured with a conductance catheter. With carotid baroreceptor feedback before bilateral cervical vagotomy, total peripheral resistance increased (P < 0.01) and mean arterial pressure decreased (-9.8 +/- 4.3 mmHg) in response to PEEP. With no feedback after vagotomy, mean arterial pressure decreased to a greater extent (-45 +/- 6 mmHg, P < 0.01), and total peripheral resistance decreased (P < 0.05) in response to PEEP. In contrast, cardiac index decreased similarly during PEEP (P < 0.01) for all baroreceptor and vagal inputs. This response comprised a decrease in the passive phase of right ventricular filling (P < 0. 01) that was not matched by the estimated increase in active right atrial output. Although the carotid baroreceptor reflex and vagally mediated mechanisms elicit vasoconstriction to compensate for the effects of PEEP on the arterial pressure, these processes fail to defend cardiac output because of the profound effect of PEEP on the passive filling of the right ventricle.

Fetal foot length: relationship to menstrual age and fetal measurements in the second trimester.

The purpose of this study was to describe the ultrasonic measurement of fetal foot length and to develop mathematical models to quantify the relationships between menstrual age and commonly measured fetal structures. We evaluated 120 patients with known last menstrual periods and normal pregnancies to develop a cross-sectional study population. All patients had ultrasonic measurement of the fetal foot length, biparietal diameter, head circumference, abdominal circumference, and femur length. Least-squares estimation of linear models was used to select the best mathematical models to describe the relationship between menstrual age and fetal foot length. A similar evaluation of the relationship between fetal foot length and the other measured parameters was performed. All models were best described by a linear equation. An R2 value of 0.94, with a standard error of the estimate of 0.204, was obtained for menstrual age versus fetal foot length. When the model for fetal foot length and menstrual age was compared with published anatomical data, close agreement was seen over the time interval studied. Our results suggest that the measurement of fetal foot length with ultrasound gives a reliable assessment of anatomical fetal or neonatal foot length and is highly correlated to the menstrual age of the fetus.

The isolated choroid plexus cyst.

OBJECTIVE: To describe the karyotypes of a population of fetuses with choroid plexus cysts and compare affected fetuses with and without additional ultrasonographic findings. METHODS: The study population included all patients undergoing second-trimester ultrasound examination in a prenatal diagnostic program between January 1993 and October 1995. The records of all cases in which a choroid plexus cyst was found were reviewed, and information was abstracted regarding the fetal karyotype and the presence of other sonographic abnormalities. RESULTS: Two hundred ten cases of choroid plexus cysts were identified among 7617 patients (2.8%) who underwent second-trimester ultrasound examination. The majority of the cases (181, or 86%) involved isolated choroid plexus cysts and the remaining 29 (14%) were associated with additional ultrasonographic findings. Autosomal aneuploidy was found in one patient with an isolated choroid plexus cyst (trisomy 21) and in another with additional findings (trisomy 18); the mothers of both of these patients were at least 35 years old. For those fetuses with known outcome, the risk of aneuploidy with isolated choroid plexus cyst (one in 180) was not statistically significantly different from that associated with choroid plexus cyst accompanied by other sonographic findings (one in 26). More than 1000 fetuses with choroid plexus cysts would have to be studied to determine whether such a difference was real. CONCLUSION: Because of the rarity of aneuploidy, the reported risk for a fetus with an isolated choroid plexus cyst must be interpreted cautiously and should include the baseline risk.

Determinants of utilization of Tay-Sachs screening.

OBJECTIVE: To identify the characteristics of patients associated with optimal utilization of Tay-Sachs screening. METHODS: Medical records of patients undergoing amniocentesis for genetic diagnosis were reviewed. Three hundred twenty-nine of 537 charts evaluated were from individuals at risk for Tay-Sachs heterozygosity. Among these, 213 couples had previously been screened for Tay-Sachs. In 116 couples, neither member of the couple had been screened before amniocentesis. A concurrent reference group consisted of 208 couples without an indication for Tay-Sachs screening. Patient characteristics, including ethnicity, genetic screening history, parental ages, and pregnancy history, were reviewed for each group. Analysis of variance and likelihood chi 2 test were used for statistical analysis. RESULTS: There were no significant differences in maternal age or reproductive history among the groups. The most common indication for amniocentesis was advanced maternal age for all three groups. However, the previously screened group was more than twice as likely to self-refer because of a positive family history or patient anxiety than was the unscreened group (P = .006). Conversely, the unscreened group was more than twice as likely as screened couples to be referred because of a positive high or positive low maternal serum alpha-fetoprotein level (P = .002). CONCLUSION: Despite 2 decades of professional and lay education, many couples are unaware of their individual risk for Tay-Sachs heterozygosity. Additional education, most likely at the professional level, is needed to maximize informed participation.