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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.

Under the auspices of the Howard Hughes Medical Institute, a set of consensus guidelines for Radiation Protection Practices has been developed for biomedical research using radioactive materials. The purposes of the guidelines are (1) to promote good radiation protection practices consistent with the needs of biomedical research, the ALARA principle, and regulatory requirements; (2) to establish common goals and consistent practices within radiation safety programs; and (3) to build a meaningful partnership between radiation safety professionals and the biomedical research community. These practices are intended to enhance radiation protection and the efficiency of the research staff. The consensus guidelines will lessen the variability in radiation safety practices that is evident among many academic research institutions and will encourage better acceptance and regulatory compliance by users of radioactive materials in biomedical research.

Previously, we identified the presence of a circulating shock protein (CSP) in the plasma of hemorrhaged rats that depolarizes a variety of cells in vitro. In isolated perfused rat hearts, partially purified CSP produced dose-dependent decreases in contractility and heart rate associated with an increase in coronary perfusion pressure (CPP). Electrical pacing failed to prevent the negative inotropic effects. Preventing the coronary vasoconstriction with nitroglycerin or attenuating it with a cyclooxygenase inhibitor also failed to prevent the inotropic or chronotropic effects of CSP. Carbocyclic thromboxane A2 (50ng/min) caused a similar increase in CPP to CSP but had no effect on contractility or rate during the first minute of infusion. These data indicate that the protein that appears in rat plasma after hemorrhage produces negative inotropic and chronotropic effects on the isolated heart that are independent of changes in CPP. Vasoactive arachidonic acid metabolites elicited by CSP are partially responsible for the increase in coronary vascular resistance.

Objective: To determine the distribution of nuchal skinfold thickness in normal and Down syndrome pregnancies and to evaluate the use of this sonographic measurement as a screening test for fetal Down syndrome., Methods: A prospective, multicenter, population-based study was performed by experienced obstetric sonographers on 1382 women with sonographically normal fetuses undergoing second-trimester amniocentesis for the indication of advanced maternal age. A standard, well-defined sonographic image was obtained at all collaborating centers. The distributions of nuchal skinfold thickness were compared between euploid and Down syndrome fetuses., Results: There were 1346 chromosomally normal pregnancies, 13 fetuses with Down syndrome (1:106), and 23 other chromosome abnormalities. Seventeen fetuses had measurements of 6 mm or greater, and one of these had Down syndrome. The median nuchal skinfold thickness in Down syndrome was 3.2 mm and in euploid fetuses was 3.1 mm. By the Mann-Whitney rank-sum test, there was no statistically significant difference in nuchal skinfold between the euploid and Down syndrome fetuses (P = .5). Overall, using a nuchal skinfold thickness of 6 mm or greater as a screening test, the detection rate for Down syndrome was one of 13 (8%), the false-positive rate was 16 of 1382 (1.2%), the positive predictive value was one of 17 (6%), and the probability of detecting Down syndrome was 6.5%., Conclusion: In this investigation, excess nuchal skinfold thickness was a poor and unreliable screening test for Down syndrome.

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.

The authors have reported previously that small-volume resuscitation (1.8 x bled volume) with 0.9% NaCl restores blood volume and attenuates hormonal responses after large hemorrhage without correction of arterial hypotension. The authors studied the role of rate of infusion in this observation in chronically prepared dogs (aortic flow probe, right atrial pressure and volume, and arterial catheters) after 30% hemorrhage (24.1 +/- 0.4 mL/kg). After 30 minutes, subjects were observed either without treatment (no resuscitation) or with infusion of 43 mL/kg 0.9% NaCl over 3 hours by one of three protocols: (1) impulse infusion over 10 minutes, (2) variable rate infusion, bolus with tapering infusion, or (3) constant rate infusion. Significant improvement in cardiac output and in blood volume and significant decreases of vasopressin and arterial catecholamines were observed in all fluid-treated groups. This benefit was relatively independent of rate of infusion, although impulse infusion produced greater early improvement, which dissipated with time, and constant rate infusion produced better late results. In none of the fluid-treated groups were these improvements reflected in improved mean arterial pressure compared with the no resuscitation group. The authors conclude that small-volume, slow-rate saline infusion produces physiologic benefits that cannot be assessed by easily measured clinical parameters. Thus, early resuscitation after trauma could aid patients even if arterial pressure is unchanged. This benefit might be even greater in patients with uncontrolled bleeding because arterial pressure, and hence bleeding, may not be increased by resuscitation of this type. A reassessment of the value of prehospital fluid resuscitation in the injured patient is warranted.

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.

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 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.

Glucagon has been implicated in the hormonal-metabolic response to injury and in the restitution of blood volume. Evidence for this has been obtained largely from observations of peripheral glucagon concentrations. The secretory response to mild or moderate hemorrhage remains undefined. Experiments have been conducted in conscious dogs surgically prepared with indwelling catheters in the portal vein (PV), femoral artery (FA), and femoral vein (FV). In addition, electromagnetic flow probes were placed about the PV and the hepatic artery (HA). Animals were subsequently subjected to either a 10% (7.5 ml/kg), 20% (15 ml/kg), or 30% (22.5 ml/kg) 3-min hemorrhage. The portal venous delivery rate (PVDR) of immunoreactive plasma glucagon (IRG), portal venous IRG concentration (PVIRG), and peripheral arterial IRG (AIRG) demonstrated variable changes following hemorrhage. When hemorrhage resulted in marked deterioration in PVBF, then PVDR did not correlate with either changes in PVIRG or AIRG. These preliminary results suggest that inferences regarding changes in PVDR of IRG cannot reliably be based solely on changes in hormonal concentrations, especially when measured only in the periphery. Moreover, since marked increases in peripheral plasma glucose levels were observed at times when PVDR of IRG was severely depressed following 20% and 30% hemorrhage it is suggested that glucagon may not play the dominant role in the early hyperglycemic response to hemorrhage.

Previous studies have suggested that increases in extracellular osmolality mediate a shift of intracellular fluid into the interstitium following 10% hemorrhage. This unidirectional fluid movement is required for full restitution of blood volume (BV) and for cardiovascular stabilization. The extent to which this mechanisms acts in larger hemorrhages was examined in these studies. Forty-two dogs were studies 3 weeks after splenectomy. Twenty were anesthetized with pentobarbital, the others were studied awake. Hemorrhages of 10% (7.5 ml/kg, 15 dogs), 20% (15 ml/kg, 13 dogs), and 30% (22.5 ml/kg, 15 dogs) were carried out over 3 minutes. Patterns of changes in osmolality, total plasma protein content, and blood volume were identical in the two groups, although osmolality was significantly greater during the first 2 hours in anesthetized dogs. Osmolality increased with increasing degrees of hemorrhage, providing an increasing driving force for fluid shifts. Restitution of BV was significantly greater after 20% hemorrhage than after 10% hemorrhage. However, restitution of BV after 30% hemorrhage was no greater than after 10% hemorrhage. Patterns of protein restitution paralleled changes in BV. Cunningham, Shires, and Wagner (7) reported fluid shifts into cells after a 30% hemorrhage associated with a fall in membrane potential. It thus appears likely that a fluid shift out of cells in response to increased osmolality is offset by shifts into cells as the magnitude of hemorrhage becomes large. This failure of homeostatic restoration of BV with consequent failure of cardiovascular stabilization may represent an early event in the development of hemorrhagic shock.