Fetal ultrasonography: normal biometric ranges in the baboon (Papio hamadryas).

Normal biometric ranges for fetal growth in a captive breeding baboon (Papio hamadryas) colony are described. Measurements include crownrump length, biparietal diameter, binocular distance, head circumference, abdominal circumference, femur length and amniotic fluid index. The pattern of fetal growth is compared with other baboon subspecies and man. The uses and limitations of such data for breeding colony management and optimum utilisation of experimentally derived data are discussed.

Brainstem auditory evoked response development in preterm and term baboons (Papio hamadryas).

Brainstem auditory evoked responses were recorded longitudinally from 11 neonatal baboons (Papio hamadryas), 6 of which were preterm. Recordings were made in unsedated animals from day 161 to day 362 after conception (term = 182 days). The pattern of development of both waveform morphology and of wave latency was consistent with that seen in the human neonate, with a rapid maturation of the response during the perinatal period, and then a slower development to adult values. Brainstem conduction time was measured from the wave I to wave IV interval, and this demonstrated a similar pattern, with a rapid decrease in latency up to term, and then decreasing more slowly to reach adult values by 4 months of age in the baboon.

Fetotoxicity of angiotensin-converting enzyme inhibition in primate pregnancy: a prospective, placebo-controlled study in baboons (Papio hamadryas).

OBJECTIVES: Serious concerns have been raised about angiotensin-converting enzyme inhibition in pregnancy. The central question remains: does toxicity of angiotensin-converting enzyme inhibition pertain to pregnant humans? STUDY DESIGN: A prospective, placebo-controlled study was performed to investigate the effect of angiotensin-converting enzyme inhibition on pregnancy outcome in the baboon. Subjects (N = 12) received active and placebo treatments sequentially in a crossover protocol. Data were analyzed with two-sample t tests, analysis of variance, Fisher's exact test, or Kaplan-Meier survival analysis, where appropriate. RESULTS: Chronic administration of enalapril (7.5 mg per day) from before conception achieved moderate but sustained angiotensin-converting enzyme inhibition as determined by repeated measures of renin-angiotensin system parameters (serum angiotensin-converting enzyme activity, plasma renin activity and plasma angiotensin I, angiotensin II, and aldosterone concentrations). Serum angiotensin-converting enzyme activity was significantly reduced throughout (< 10 nmol.ml-1.min-1, p < 0.01), with significant increases in plasma renin activity and angiotensin I (p < 0.01). Angiotensin II and aldosterone were maintained unchanged compared with placebo. There was a significant incidence of fetal death or intrauterine growth retardation in fetuses exposed to enalapril (eight of 13, zero on placebo, p < 0.01). When the definition of adverse pregnancy outcome was restricted to fetal death alone (four of 13) the difference remained significant (p < 0.05). Maternal arterial pressure was unchanged before conception, but a small and significant fall (10 to 15 mm Hg, p < 0.01) was detected throughout pregnancy. There was no fetal malformations. CONCLUSION: The study provides definitive evidence for serious consequences of angiotensin-converting enzyme inhibition in pregnancy of high-order primates.

Haemodynamic actions of a nitric oxide (EDRF) synthesis inhibitor in conscious baboons (Papio hamadryas).

1. The haemodynamic effects of intravenous nitric oxide inhibitor, N-nitro-L-arginine (NOLA), were examined in four conscious non-restrained baboons (Papio hamadryas). Mean arterial pressure, (MAP), systemic vascular resistance (SVR) and cardiac output (CO) were measured at timed intervals up to 24 h after a bolus injection of NOLA. 2. N-nitro-L-arginine increased blood pressure in a dose-dependent manner up to 9.5 mg/kg. Increases in blood pressure were accompanied by increases in SVR and decreases in CO, with a significant fall in heart rate. 3. One animal received 9.5 mg/kg NOLA and became unconscious, suggesting cerebral vasospasm. 4. Vascular effects of nitric oxide contribute significantly to the regulation of arterial blood pressure under physiological conditions in the baboon.

Helminthic infestation complicated by intussusception in baboons (Papio hamadryas).

Two juvenile baboons presented with diarrhoea, which did not resolve completely following antibiotic therapy. Ileal intussusception was identified at autopsy in both cases. Trichuris was the only gastrointestinal pathogen for which evidence could be found. This helminth is well-recognized as a cause of intussusception in human infants, but the complication has not been reported previously in non-human primates. It is likely to be fatal if undiagnosed.

Corticotropin-releasing hormone in baboon pregnancy.

During human pregnancy, plasma CRH immunoreactivity (CRH-IR) rises progressively, peaking during labor and falling after delivery. Among animal species, only higher primates have elevated CRH-IR during pregnancy. This study examines whether changes in plasma CRH-IR in the baboon (Papio hamadryas) are similar to those in the human. CRH-IR was determined by RIA in 16 baboons at different stages of gestation (44 samples) and in 3 males. Assays were performed on Vycor extracts of plasma and CRH-IR diluted in parallel to synthetic human (h) CRH-41 standard. Reverse phase high pressure liquid chromatography and size-exclusion chromatography with Sephadex G-50 showed that baboon CRH-IR eluted in a position similar to that of hCRH-41. Regression analysis revealed a cubic association between plasma CRH-IR and gestational age, with peak concentrations occurring at 60 days gestation (term = 182 days). Although greatly elevated concentrations persisted throughout pregnancy, concentrations in the first half (1-91 days) were significantly higher (mean +/- SEM, 1.9 +/- 0.3 nM/L; n = 27) than in the second half (92-182 days; 1.0 +/- 0.2 nM/L; n = 11; P < 0.003 by t test). CRH-IR fell to low levels by day 1 postpartum. The concentration of total cortisol in nonpregnant animals was 1370.9 +/- 134.9 nM/L (n = 5), which was similar to pregnancy levels (1346.3 +/- 356.1 nM/L; n = 28); there was no gestational age-related pattern evident. Plasma corticosteroid-binding globulin was estimated by RIA, and plasma free cortisol was calculated to be 73 +/- 14 nM/L in pregnant animals and showed no gestational age-related changes. The mean progesterone concentration in the pregnant baboon was 12.5 +/- 2.2 nM/L (7-169 days; n = 27). There was no significant change in progesterone levels during the period of gestation studied; however, they were higher than nonpregnant levels. Baboon and human plasma (0.1 mL each) were incubated with [125I]Tyr-hCRH in Tris-HCl buffer (pH 7.5) and chromatographed with Sephadex G-75, using the same buffer. The radioactivity of fractions was determined, and no CRH-binding protein was identified in baboon plasma. This study indicates that gestational changes in CRH-IR in the baboon are different from those observed in humans. There is a dissociation between maternal plasma CRH and cortisol. The apparent lack of bioactivity of baboon plasma CRH is not due to a circulating binding protein, which is absent in this species.

Preclinical evaluation of 99m technetium-labeled DD-3B6/22 Fab' for thrombus detection.

Injection of 99mTc-labeled Fab' fragments of the anti-fibrin antibody DD-3B6/22, in the baboon, resulted in clear visualisation of both fresh and aged autologous thrombi by gamma scintigraphy. Whole body scintigraphy, pharmacokinetics and urine analysis showed rapid renal excretion of the conjugate with little accumulation of label in other organs. 99mTc-DD-3B6/22 Fab' appears a suitable candidate for further investigation as a radioimaging agent for thrombi in humans.

Early blood pressure control improves pregnancy outcome in primigravid women with mild hypertension.

OBJECTIVE AND DESIGN: The aim of this study was to evaluate treatment of mild to moderate hypertension (less than 170/110 mmHg) in pregnancy in a prospective, randomised, double-blind trial. SETTING AND PATIENTS: Pregnancy outcome was studied for 52 primigravid women, managed in hospital from early in the third trimester. INTERVENTIONS: Patients were randomly allocated either to placebo or to active treatment (clonidine plus hydralazine). MAIN OUTCOME MEASURES AND RESULTS: Maternal deterioration dictated withdrawal from trial therapy for eight patients receiving placebo, but for only one receiving active treatment. Maternal proteinuria occurred only in the placebo group. Intention-to-treat analysis showed a significant increase in premature delivery for complications in the placebo group (P less than 0.05), despite active blood pressure treatment for those withdrawn from the group because of severe hypertension (170/110 mmHg or higher). Neonatal respiratory distress requiring intensive care occurred only in babies born to women in the placebo group. There were no perinatal deaths and no adverse effects of treatment in the neonates. CONCLUSIONS: The study indicates that early control of mild hypertension in pregnancy can prevent progression to emergency premature delivery.

Highly vectorial secretion of inhibin by primate Sertoli cells in vitro.

Having recently demonstrated highly vectorial and FSH-stimulated inhibin secretion by immature rat Sertoli cells in vitro, we wished to determine if vectorial secretion of inhibin was also characteristic of primate Sertoli cells. By adapting techniques for isolation of Sertoli cells from testes of the immature rat and cynomolgus monkey. Sertoli cells were isolated from immature baboon testes. Sertoli cells were then plated onto matrix-impregnated porous filters and cultured in twin chamber assemblies in fully defined, supplemented HEPES-buffered Eagles medium. Inhibin was measured in conditioned culture media by an heterologous RIA validated for primate inhibins. Throughout 28 days of culture immunoreactive inhibin was readily detectable in the upper chambers whereas inhibin was undetectable or just detectable in the lower chambers. The median ratio of upper to lower chamber inhibin content was 15.3 under basal conditions rising to 41 under FSH stimulation. Inhibin secretion into the upper chamber was increased 2.5 +/- 0.4 times by stimulation with ovine FSH (100 ng/ml). We conclude that immature Sertoli cells from a nonhuman primate demonstrate FSH-responsive and highly vectorial secretion of inhibin almost exclusively into the upper chamber. These data suggest that during maturation mammalian Sertoli cells secrete inhibin vectorially mainly from the apical surface of the cell towards the seminiferous tubular lumen. The predominance of inhibin secretion into the seminiferous tubule during testicular maturation suggests that inhibin may have an important paracrine or autocrine role in the developmental biology of spermiogenesis.

Hemodynamics of conscious unrestrained baboons, including cardiac output.

A method is described for comprehensive hemodynamic study of undisturbed baboons (Papio hamadryas) that incorporates cardiac output measurement by thermodilution. Instrumentation includes arterial, aortic, and central venous catheterization by a surgical technique that does not require entry to peritoneal or thoracic cavities. It provides a means for right atrial indicator delivery with aortic temperature recording of thermodilution curves. Accuracy was confirmed by comparison to measurement by Swan-Ganz catheters. Diurnal variations of systemic arterial pressure in long-term study of conscious baboons were shown to result from significant increases in cardiac output by day (P less than 0.001), despite concomitant falls in systemic vascular resistance. The cardiac output values obtained were 0.13 l.min-1.kg-1 at night and 0.16 l.min-1.kg-1 by day. Comparison of these results to previous reports of cardiac output in baboons highlights the inadequacies of methods that require physical restraint or anesthesia. This technique also leaves the baboons intact for subsequent breeding or experimental use after catheter removal without the need for further surgery.

Gastric haemorrhage and perforation caused by a trichobezoar in a baboon (Papio hamadryas).

A captive-bred male baboon presented with severe evidence of blood loss and melaena. An upper gastrointestinal radiological study with Gastrografin showed a large trichobezoar. Laparotomy confirmed its presence and revealed gastric ulceration with perforation and generalized peritonitis. The condition was successfully treated by surgery.

Effect of angiotensin II on baroreceptor reflex control of heart rate in conscious baboons.

Studies of the baroreceptor-heart rate reflex were performed in four conscious, unrestrained male baboons to determine whether changes in circulating angiotensin II within the physiological range are associated with alterations in baroreceptor reflex sensitivity. With the animals on a high sodium intake, studies were performed before and during graded angiotensin II infusion (10 and 20 ng/kg/min). To separate effects on baroreceptor reflex function mediated by angiotensin II-induced increases in arterial pressure, these studies were repeated on a different day with simultaneous glyceryl trinitrate infusion to prevent increases in pressure during angiotensin II infusion. With the animals on a low sodium intake, studies were performed before and after angiotensin converting enzyme inhibition with captopril (1 and 5 mg/kg). These studies were also repeated on a separate day during simultaneous phenylephrine infusion to prevent a decrease in pressure with captopril. Reduction in sodium intake had no significant effect on arterial pressure, heart rate, or plasma volume, although arterial plasma angiotensin II concentration and renin activity were significantly increased (p less than 0.01). Infusion of angiotensin II produced a significant reduction in baroreceptor reflex sensitivity (p less than 0.01), and converting enzyme inhibition produced a significant increase (p less than 0.05). These effects accompanied significant increases and decreases in arterial angiotensin II concentration, respectively (p less than 0.01), but were independent of angiotensin II-related changes in arterial pressure. The data indicate that physiological variations in circulating angiotensin II have a direct effect on sensitivity of the baroreceptor-heart rate reflex.

Group housing of hamadryas baboons: a new cage design based upon field studies of social organization.

The hamadryas subspecies, which is utilized extensively for laboratory research, has a social structure unique among baboons. Field studies have shown that small one male units are the basic grouping in a complex multi-level social system. A housing design for a research colony of hamadryas baboons was conceived to reflect this unique social organization and related behavioral patterns. The outcome of combining such ethological considerations with practical dictates for housing large laboratory primates has been assessed in terms of reproductive performance, animal health and utilization for research. Various benefits of this approach to cage design for hamadryas baboons are identified in this report.

Circulatory adaptation to pregnancy--serial studies of haemodynamics, blood volume, renin and aldosterone in the baboon (Papio hamadryas).

To test the hypothesis that haemodynamic changes in pregnancy precede any significant increase in circulating blood volume, serial haemodynamic studies were performed in eight baboon pregnancies using Swan-Ganz catheterization and arterial cannulation. Simultaneous measurements were made of red cell and plasma volumes, and of plasma renin activity and aldosterone concentration. Haemodynamic changes identified by 4 weeks gestation included significant (P less than 0.01) reductions in right atrial pressure, systemic and pulmonary arterial pressures, and systemic and pulmonary vascular resistance. Stroke volume increased in early pregnancy (P less than 0.01), with a consequent increase in cardiac output. Plasma renin activity and aldosterone concentration were elevated by 4 weeks (P less than 0.01), but plasma volume did not expand until 12 weeks. At no stage in middle or late pregnancy was cardiac filling pressure increased. These results provide the first haemodynamic evidence that pregnancy is a state of reduced effective blood volume associated with vasodilatation from the early weeks.

Nonocclusive chronic vascular catheterization of conscious unrestrained baboons.

A surgical technique is described for chronic arterial and venous catheterization of unrestrained adult baboons. Vascular access was achieved through a small (5 cm) abdominal incision and an extraperitoneal approach to the iliac vessels, which minimizes postoperative morbidity, discomfort, and restriction of movement. The method permits secure but nonocclusive catheterization, confirmed by angiography. Catheters were removed without further surgery, leaving the baboons intact for reuse. Catheters placed in the distal common or proximal external iliac vessels were all patent when removed at 46-61 days. The results demonstrate arterial pressure, pulse rates, drug administration, blood sampling, and plasma volume measurement as examples of the technique's application in conscious unrestrained baboons.

Blood volume measurement in baboons: simultaneous estimation of red cell volume and plasma volume.

A method is described for frequent sequential blood volume estimation in baboons using 32P for red cell volume measurements and 125I-albumin for simultaneous plasma volume measurements. Values for red cell, plasma, and total blood volumes are reported. Close correlations of the volumes to bodyweight were demonstrated. Circulatory half-lives of the isotopes, determined from disappearance curves, confirmed their suitability for serial measurements in these baboons.