Adult Male Baboons Research Articles

Local infusion of heparin reduces anastomotic neointimal hyperplasia in aortoiliac expanded polytetrafluoroethylene bypass grafts in baboons

Purpose: Recently, we designed and characterized a novel expanded polytetrafluoroethylene (ePTFE)-based local drug delivery approach that selectively concentrates infused pharmacologic agents specifically within those blood layers adjacent to the graft wall and at downstream anastomotic sites. In this study, we locally administrated standard heparin therapy and evaluated its effects on neointimal hyperplasia formation in a baboon model of aortoiliac bypass graft placement.Methods: Six adult male baboons underwent bilateral aortoiliac bypass grafting with ringed ePTFE (4 mm internal diameter × 5 cam length). In each animal, the distal anastomosis of one graft was continuously infused with heparin (50 U/h) and the distal anastomosis of the contralateral graft was infused with saline solution at the same rate (2.5 μL/h), with osmotic pumps implanted for 4 weeks. Platelet counts and activated partial thromboplastin time measurements were performed weekly. The specimens were harvested at 4 weeks and were subjected to morphometric analysis. Cell proliferation was assessed with bromodeoxyuridine immunostaining.Results: All the harvested grafts were patent except for one control graft. There were no significant differences in platelet counts or activated partial thromboplastin time measurements taken before and during heparin infusion. As expected, there were no significant differences in graft neointimal hyperplasia and cell proliferation at the proximal anastomoses between the heparin-infused and control grafts. In contrast, at the treated distal anastomoses, heparin infusion significantly reduced the graft neointimal area by 65% and the cell proliferation index by 47% as compared with the untreated control distal anastomoses.Conclusion: These results show that local infusion of heparin significantly reduces distal anastomotic neointimal hyperplasia and cell proliferation without measurable systemic anticoagulation or other side effects. Thus, this approach may represent an attractive strategy for prolonging ePTFE bypass graft patency.

Food and cocaine self-administration by baboons: effects of alternatives.

The effects of the availability of an alternative reinforcer on responding maintained by food pellets or drug solutions were examined in 8 adult male baboons (Papio hamadrayas anubis). During daily 23-hr experimental sessions, baboons had access to both food pellets and fluid under a two-choice procedure, in which the response requirement, under a fixed-ratio schedule, differed for the two commodities. There were no restrictions on access to water, which was continuously available from a spout at the rear of each cage. In Experiment 1, the fixed-ratio requirement, or cost, for fluid delivery remained constant while the fixed-ratio requirement for pellets was changed every 2 or 3 days when (a) no fluid, (b) a dilute dextrose vehicle, (c) 0.008 mg/kg per delivery cocaine, (d) 0.016 mg/kg per delivery cocaine, or (e) 0.032 mg/kg per delivery cocaine was available concurrently. In Experiment 1, progressively increasing the response requirement for pellets decreased pellet intake, but for 4 baboons pellet intake at maximum pellet cost was lower when cocaine, compared to the vehicle, was available. Increasing the response requirement for pellets had variable effects on vehicle intake. However, increasing the response requirement for pellets increased intake of at least one dose of cocaine to a greater extent than vehicle in all 8 baboons. Thus, cocaine could be considered a more effective economic substitute than vehicle for pellets. Experiment 2 systematically varied the order in which the response requirements for a pellet delivery were presented and added a control condition in which cocaine doses, yoked to the amount self-administered, were given three times during the session by the experimenter. Again, pellet intake at maximal pellet cost was lower when cocaine, compared to the vehicle, was available. In contrast, experimenter-given cocaine doses did not alter responding maintained by pellets. Thus, the effects of self-administered cocaine on responding maintained by food pellets differed from the effects of experimenter-given cocaine on responding maintained by food pellets.

EFFECT OF ISOFLURANE ON EPIDURAL RESPONSES OF POSTERIOR TIBIAL SOMATOSENSORY EVOKED POTENTIALS IN THE BABOON

S198 INTRODUCTION: Somatosensory evoked potentials from posterior tibial nerve stimulation (ptn-SSEP) have been utilized intraoperatively to assess spinal cord viability during spinal surgery. Stimulation produces an ascending volley of activity that can be recorded along the neural pathway. Previous studies have shown that inhalational anesthetics depress cortical SSEP responses making subcortical responses a desirable recording location. In order to better understand the mechanisms of anesthetic depression, this study was conducted utilizing epidural catheter recordings in a baboon. METHODS: Adult male and female baboons (19-24 Kg) with clinically and electrophysiologically normal nervous systems were studied in this institutionally approved animal protocol. Animals were anesthetized with isoflurane (ISO) following initial anesthesia with intramuscular ketamine (10 mg/kg). Blood pressure, pulse, oxygen saturation, esophageal temperature and end-tidal gases were monitored and the lungs ventilated through endotracheal tubes placed in the trachea. ptn-SSEP responses were produced by 300 microsecond square wave pulses at 5.7 Hz and 2 times the motor threshold to the posterior tibial nerve at the ankle. Recordings were made from a thoracic epidural catheter with 1 cm2 electrodes spaced 3 cm apart using amplification of 10,000 and band pass filtration of 100-3000 Hz. Triplicate recordings were taken after 30 minute equilibration at end-tidal concentrations of ISO of 0.3,0.6,0.9,1.2,1.5,1.8,2.1 % (initial recordings taken over 2 hours after initial ketamine). The onset and amplitude of the response complex was measured for each average of 200 stimulations. Dunnets test was used to examine for statistically significant deviations from 0.3% ISO (p < 0.05). RESULTS: Plotted below is the latency (Left) and amplitude (right) of the responses. Statistically significant deviations were observed for response onset at higher ISO concentrations, but not for response amplitude. (Figure 1)Figure 1DISCUSSION: These results are consistent with an effect on neural conduction in the peripheral nerve and/or spinal cord and suggest the major anesthetic depression reflected in cortical recordings occurs more cephalad.

The origin and pattern of distribution of the posterior intercostal arteries in the baboon (Papio ursinus).

The posterior intercostal arteries of six female and four adult male baboons (Papio ursinus) were investigated by latex injection and subsequent dissection to determine their origin and pattern of distribution. Basic morphological and functional similarities with that of man could provide some base-line data pertinent to future experimental studies in the areas of thoracic aortic aneurysm and aortic atherosclerotic lesion in man. Basic similarities were observed between the baboon and man in the number of intersegmental arteries, the origin of the first two pairs of posterior intercostal arteries, and the anastomosis between the superior intercostal and the third posterior intercostal arteries. However, the baboon showed a craniocaudal sequence of paired orifices giving rise to paired arteries; orifices with incompletely divided septum giving rise to paired arteries; single orifices leading to a common trunk, which finally gives rise to paired arteries; and single orifices opening into single arteries. In addition, there was a craniocaudal decrease in the distance between any given pair of intercostal arteries and an increase in the spacing between adjacent pairs of intercostal arteries. Where a single artery supplied one side of the intercostal space, the contralateral side received a collateral branch, either from the preceding or succeeding intercostal artery. Though the basic organisation of the origin and distribution of the posterior intercostal arteries in the baboon is similar to that of man, the differences observed in the baboon might be attributed to factors such as body size, mode of activity, and even the phylogenetic level of development of the baboon.

The absence of a triphasic renovascular response by the multicalyceal kidney of the primate in reaction to acute, complete, unilateral, ureteric obstruction.

The early renovascular response by the ipsilateral kidney to acute, total, unilateral, ureteric obstruction was investigated in the adult male chacma baboon (Papio ursinus). Complete occlusion was effected by ligating the ureter at the brim of the bony pelvis ("N"=10). Sham studies were enacted using the same method but the ureter was not obstructed ("N"=11). Haemodynamic reactions were monitored for 12 hours. Compared with the sham-occluded set, the renal pelvic pressures in the obstructed group were significantly increased (P<0.05) from the second hour of the inquiry. However, there were no significant differences in renal blood flow, either between or within the respective cohorts. In this study, the renovascular response to acute ureteric occlusion was similar to that displayed by the multicalyceal kidney of other species under identical conditions. This reaction was fundamentally different to that exhibited by the unicalyceal kidney under similar circumstances.

Retrograde transvenous neuroperfusion: a back door treatment for stroke.

Stroke is the third leading cause of death and the leading cause of adult disability in the United States. The clot-lysis drug tissue plasminogen activator is the only treatment that has been effective for acute stroke patients, yet there are significant limitations to its use and effectiveness. In this study retrograde transvenous neuroperfusion (RTN) was evaluated for its efficacy in reversing acute ischemia, preventing paralysis, and limiting pathological evidence of infarction in baboons. Ten adult male baboons underwent 3.5 hours of reversible middle cerebral artery occlusion (MCAO) under isoflurane (0.25% to 1.5%) anesthesia. Five randomly chosen animals received RTN treatment 1 hour after start of MCAO. Somatosensory evoked potentials were recorded during MCAO. Animals were assigned daily neurological scores. Animals were killed 6 days after MCAO, and brains were quantitatively analyzed for infarct volume. Within 1 hour after RTN was started, treated animals showed significantly improved somatosensory evoked potentials (103.3% versus 75% of baseline; P<0.01). Likewise, the combined neurological score for the RTN-treated group was 99.2, while the combined mean score for the untreated group was 66.4 (P<0.015). The mean infarction volume was 8.8+/-3.1% (of contralateral hemisphere) for the control group and 0.3+/-0.2% for the RTN-treated group (P<0.01). No increased mortality was seen in the RTN-treated group. We conclude that RTN treatment during MCAO effectively reverses the pathophysiological sequelae of ischemia, even when the treatment is initiated 1 hour after the onset of ischemia. Although the infarct volume in the control group was variable when quantitatively assessed 6 days after 3.5 hours of MCAO, virtually no evidence of infarcts was seen in the RTN-treated group.

Prolonged Allogeneic and Xenogeneic Microchimerism in Unmatched Primates without Immunosuppression by Intrathymic Implantation of CD34+Donor Marrow Cells

Engraftment of stem cell-enriched donor marrow implanted in the thymus of a foreign host might facilitate acceptance of donor-specific organ or tissue grafts. To test this hypothesis, allogeneic and xenogeneic CD34+marrow cells from unrelated adult male baboons and humans were injected intrathymically in eight infant female baboons, both with and without standard cyclosporine-based immunosuppression. In allogeneic experiments, male (donor) cells, of both T- and B-cell lineages, were detected by PCR in the peripheral blood of all six recipients and persisted for at least 15 months in 2/4 recipients studied longtutudinally. Donor-derived skin grafts survived twice as long as third party grafts in unimmunosuppressed recipients. In xenogeneic protocols, human male (donor) cells were demonstrable for 7 and 15 months, respectively, in two baboon recipients with evidence that implanted human CD34+cells had produced lymphoid progeny. Survival of donor-specific skin xenografts was prolonged in one of two recipients. These experiments demonstrate that the intrathymic injection of CD34+marrow cells can result in long-lasting lymphohematopoeitic microchimerism in unrelated primates even without immunosuppression and can alter donor-specific skin graft survival.

Aerosolized manganese SOD decreases hyperoxic pulmonary injury in primates. II. Morphometric analysis.

Hyperoxia damages lung parenchyma via increased cellular production of reactive oxygen species that exceeds antioxidant defenses. We hypothesized that aerosolized human recombinant manganese superoxide dismutase (rhMnSOD) would augment extracellular antioxidant defenses and attenuate epithelial injury in the lung during hyperoxia in primates. Twenty-four adult male baboons were anesthetized and mechanically ventilated with 100% oxygen for 96 h. The baboons were divided equally into four groups. Oxygen alone and oxygen plus rhMnSOD given at 3 mg . kg-1 . day-1 were compared to assess efficacy of the drug. Subsequently, aerosolized rhMnSOD was given at 1 or 10 mg . kg-1 . day-1 to study dose effects and toxicity. Quantitative morphometry showed protection of alveolar epithelium from hyperoxia by 3 mg . kg-1 . day-1 rhMnSOD (P < 0.05). In addition, interstitial fibroblast volumes were increased in the treatment group (P = 0.06). This effect appeared greater at the two higher doses of the rhMnSOD. The aerosolized drug was localized to the surface of airways and air spaces and macrophages by immunolabeling studies, suggesting efficacy via physicochemical properties that localize it to cell surfaces or by effects on alveolar macrophage function.

Food and amphetamine self-administration by baboons: effects of alternatives.

The effects of the availability of an alternative reinforcer on responding maintained by food pellets or fluid solutions were examined in 6 adult male baboons (Papio cynocephalus anubis). During daily 23-hr experimental sessions, baboons had concurrent access to both food pellets and fluid, with responding maintained under fixed-ratio schedules of reinforcement that varied between the two commodities. The fixed-ratio requirement, or cost, for pellets was increased when (a) no fluid, (b) a dilute dextrose vehicle, (c) 0.002 mg/kg d-amphetamine, or (d) 0.004 mg/kg d-amphetamine was available. When given nonrestricted concurrent access to food pellets and amphetamine at minimal cost (FR 2), baboons self-administered sufficient amphetamine to decrease pellet intake. Increasing the response requirement for pellets decreased pellet intake at a similar rate regardless of the available fluid and increased fluid intake in a variable manner among baboons such that there were no statistically significant increases in fluid intake. In contrast, when access to pellets was restricted to 70% of maximal intake under nonrestricted conditions, increasing pellet cost decreased pellet intake and increased fluid intake more rapidly when the high amphetamine dose was available. Thus, amphetamine was more effective as an economic substitute for pellets when access to pellets was restricted. The response cost for vehicle and both amphetamine concentrations was increased when baboons had nonrestricted and restricted access to pellets. Increasing the response requirement for fluid delivery decreased intake of all three fluids similarly under both pellet-access conditions. The results indicate that substitution between commodities with minimal commonalities can be studied under controlled laboratory conditions and is dependent upon reinforcement schedule and commodity restrictions.

Changes in the lung after prolonged positive pressure ventilation in normal baboons

Purpose : The effects of prolonged positive pressure ventilation on lung ultrastructure are not well defined in primates. This study was designed to measure cardiopulmonary and morphological responses to 4 days of positive pressure ventilation in normal baboons. Materials and Methods : Six adult male baboons were mechanically ventilated on air for 96 hours with 2.5 cm positive end-expiratory ventilation and a tidal volume of 12 to 15 mL/kg. Physiological measurements were obtained every 12 hours and serial measurements of ventilation-perfusion ( V A ̇ / Q ̇ ) were performed using the multiple inert gas elimination technique. Quantitative morphotometry, lung dry-to-wet ratio, and surfactant analysis were performed at the end of the experiment. Results : Cardiovascular variables, except for a small increase in mean pulmonary artery pressure at 84 and 96 hours, were not significantly affected by positive pressure ventilation. Arterial PO 2 decreased, and shunt fraction increased from 0.7% of cardiac output to 5.4% ( P < .01). Dispersion of perfusion increased threefold ( P < .01), and dispersion of ventilation doubled ( P < .01) indicating increased V A ̇ / Q ̇ mismatch. Respiratory system compliance decreased by 30% ( P < .01). There was no lung edema or change in surfactant composition. Lung morphometry showed increases in polymorphonuclear cells and type 11 cell volume. Vacuolated endothelial cells and bare basement membrane were observed consistently. Conclusion : Four days of positive pressure ventilation decreases lung compliance and worsens gas exchange by increasing shunt and V A ̇ / Q ̇ mismatch in healthy baboons. These effects are accompanied by only minor ultrastructural changes and mild inflammatory responses in the lung.

Expression Of FcγRl On Polymorphonuclear Leukocytes In A Primate Model Of Sepsis. † 1277

The type I Fc receptor for immunoglobulin G (FcγRl, CD64) is a membrane glycoprotein expressed by polymorphonuclear leukocytes (PMNs). While constitutive expression of FcγRl is minimal, rapid upregulation under the influence of inflammatory mediators (IFNg, G-CSF, GM-CSF) has been demonstrated. Early studies suggest that increased expression of FcγRl may occur during states of acute infection. To better characterize the pattem of expression of FcγRl during the PMN response to infection, we used flow cytometry to quantitate FcγRl expression in a primate model of sepsis. Under a separate protocol at the Southwest Foundation for Biomedical Research, eight healthy adult male baboons (Papio cynocephalus) received intravenous infusions of Escherichia coli. Ventilator, fluid, and pressor support were provided as needed. Blood samples for flow cytometry and complete blood count were collected pre-infusion (0 hours) and at 6, 12, 18, 24, 48, and 72 hours post-infusion. All eight animals survived to 6 hours. Two animals survived to 72 hours; the remaining six died from septic shock prior to the end of the experiment. Flow cytometry data from two animals could not be used due to lab error. Mean FcγRl expression at baseline was 7.2 ± 4.7 percent (N = 6). Six hours after starting the E coli infusion, the mean expression was 26.1 ± 8.99 percent(N = 6, p =.006 vs. 0 hrs). Mean FcγRl expression increased at each time interval in the surviving animals, to a maximum of 96.2 ± 2.0 percent(N= 2). Regression analysis demonstrated that FcγRl increased linearly with the log of time (r2 =.89, p = <.0001). Total white blood cell count, absolute neutrophil count, and immature to total neutrophil ratio did not have a linear relationship with time, but rather tended to follow a biphasic pattern. When compared to traditional clinical markers for infection, FcγRl expression was unique in its rapid and consistent response. Further studies are needed to determine the clinical usefulness of this assay.Figure

The response of group-housed baboons to three enrichment toys.

The behaviour of group-housed baboons was compared before and after the provision of durable cage toys. One adult male hamadryas baboon and 13 adult female olive baboons living in a large enclosure were observed after they were given seven nylon bones, seven Kong toys and seven Plaque Attackers. Observations were conducted four times per week on each subject over a 6-week period. Abnormal, cage-directed, inactive and self-directed behaviours all significantly decreased after the provision of the toys, while enrichment-directed activities significantly increased. Aggression did not differ between the no toy and toy conditions. Approximately 26% of the baboons were using the toys at any one time, and use of the Kong toys and the bones was higher than that of the Plaque Attackers. Individuals who used enrichment structures already present were also those who used the new toys the most.

The glomerular filtration rate, effective renal plasma flow, and renal blood flow in the adult male chacma baboon (Papio ursinus).

The radionuclide determination of glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) has been validated in man, but not in the primate. GFR, ERPF, and renal blood flow (RBF) were measured in a group of 12 adult male chacma baboons using radiopharmaceuticals. GFR was determined using 99mtechnetium-labelled diethylenetriamine-pentacetic acid. ERPF was measured with 131iodine-labelled hippuran. RBF, body surface area, and kidney weights were calculated using standard formulae. GFR was 49 +/- 11 ml/min and ERPF was 237.9 +/- 54.2 ml/min. Calculated RBF was 430.7 +/- 111.9 ml/min and 507.4 +/- 138.4 ml/min/100 g of renal tissue. The results are in agreement with those obtained using more laborious nonradioisotopic techniques such as para-aminohippurate (PAH) and creatinine clearance and could serve as baseline normal values in the adult male chacma baboon.

Why should an aged male baboon ever transfer troops?

Dispersals by subadult or adult male baboons are common. In contrast, the occasional transfer of aged baboons is puzzling, given the physical dangers of transfer and the cognitive demands of mastering the ecological and social rules of a new troop. The present data suggest a possible explanation for such transfers in a study of two troops of olive baboons (Papio anubis) in Kenya. Aged males who remained in the troop in which they had been dominant were subjected to significantly higher rates of approach-avoid interactions by the current high-ranking cohort (i.e., the individuals they had dominated years past) when compared to males who had transferred into the troop in their old age. Thus, transfer in old age offers the advantage of relative anonymity. Of the 14 males who progressed into older adulthood in the same troop in which they were in their prime, seven ultimately transferred to a different troop. The seven who remained and the seven who transferred did not differ in the rate at which they were subjected to approach-avoid interactions. However, those who remained had significantly higher rates of various affiliative behaviors (copulations, consortships, grooming and contact with females, and positive interactions with infants). Thus, amid the disadvantages of an old age spent in the troop in which a male baboon was in his prime, a high degree of social affiliation might constitute a sufficient disincentive against transferring. © 1996 Wiley-Liss, Inc.

Complete regeneration of bone in the baboon by recombinant human osteogenic protein-1 (hOP-1, bone morphogenetic protein-7).

We examined the efficacy of a single application of recombinant human osteogenic protein-1 (hOP-1, bone morphogenetic protein-7) for its ability to regenerate large calvarial defects in adult male baboons (Papio ursinus). Recombinant hOP-1, in conjunction with baboon or bovine guanidinium-extracted insoluble collagenous bone matrix (0.1, 0.5 and 2.5 mg per g of collagenous matrix as carrier), was implanted in 46 calvarial defects surgically prepared in 14 baboons, whilst 18 defects were implanted with the carrier matrix without hOP-1. Specimens were harvested on d 15, 30, 90 and 365 and subjected to histomorphometry on serial undecalcified sections cut at 7 microm to study the temporal sequence of tissue morphogenesis after the single application of hOP-1. Histological analysis indicated that the induction of new bone formation proceeded from the periphery to the central core of hOP-1 treated specimens after rapid angiogenesis and mesenchymal cell migration in apposition to the collagenous matrix. Whilst chondrogenesis was limited, newly formed bone has already filled with fully differentiated bone marrow elements as early as d 15, even with the 0.1 mg dose of hOP-1. On d 30 and 90, doses of 0.1 and 0.5 mg of hOP-1 showed greater amounts of bone than controls, and on d 90, they induced complete regeneration of the defects. Doses of 2.5 mg hOP-1 per g of matrix induced extensive osteogenesis initially with heterotopic ossification and displacement of the temporalis muscle above the defects. One year after implantation of hOP-1 there was restoration of the internal and external cortices of the calvaria. These results show that hOP-1 induces complete regeneration of calvarial bone in the adult primate, and suggest that the optimal activity of hOP-1 to achieve regeneration is between 100 and 500 microg of hOP-1 per g of matrix. These results in the primate may form the scientific basis for future clinical applications of hOP-1.

PEG-BP-30 Monotherapy Attenuates the Cytokine-Mediated Inflammatory Cascade in Baboon Escherichia coli Septic Shock

Septic shock following gram-negative infection is a leading cause of mortality in critically ill patients, accounting for nearly 200,000 deaths a year. The exaggerated production of tumor necrosis factor-α (TNFα) is known to contribute to hemodynamic collapse and the hematological dyscrasia associated with gram-negative sepsis. Although previous studies have shown TNFα antibodies and TNF immunoadhesins to be effective in experimental gram-negative sepsis, we postulated that administration of a novel construct of two modified soluble p55 receptors linked to polyethylene glycol (PEG-BP-30) would also attenuate the hemodynamic and hematologic alterations to lethal Escherichia coli septic shock in nonhuman primates. Nine adult female and male baboons ( Papio anubis), weighing 10-17 kg, were anesthetized and invasively monitored. The nine animals were randomized to receive either 0.2 mg/kg body wt PEG-BP-30 ( n = 3), 5.0 mg/kg body wt PEG-BP-30 ( n = 3), or placebo ( n = 3). One hour after pretreatment, animals were infused with 5-10 × 10 10 CFU/kg of live E. coli iv and vital signs were recorded for the next 8 hr. Arterial blood was drawn for baseline parameters and throughout the study to obtain total and differential white blood cell and platelet counts and cytokine levels (TNFα, IL- 1β, IL-6, IL-8). E. coli bacteremic baboons receiving only placebo demonstrated a significant fall in mean blood pressure and leukopenia. Two of the three animals expired. In contrast, five of the six baboons receiving the PEG-BP-30 survived and these animals exhibited markedly attenuated declines in blood pressure and leukocyte numbers. Septic baboons also manifested monophasic plasma TNFα, IL-1β, IL-6, and IL-8 responses that were significantly attenuated by PEG-BP-30 pretreatment in a dose-dependent manner. We conclude from these data that the administration of PEG-BP-30 improves survival and attenuates the TNFα-mediated pathophysiology in E. coli sepsis.

A non-human primate study (baboon; Papio hamadryas) to determine if a long-acting progestogen, levonorgestrel butanoate, combined with a long-acting androgen, testosterone buciclate, can suppress spermatogenesis: I. Dose-finding study.

This study in adult male baboons was conducted to establish the dose of a long-acting progestogen, levonorgestrel butanoate, and that of a long-acting androgen, testosterone buciclate, which, when combined, would achieve optimal and prolonged suppression of spermatogenesis. Two intramuscular injections of levonorgestrel butanoate at 3-month intervals and in the dose range 1-8 mg/kg reduced sperm production and plasma concentrations of testosterone, LH and FSH for periods of up to 6 months. The suppression of sperm production was greatest and most prolonged in the 4 mg/kg group. Two intramuscular injections of testosterone buciclate at 3-month intervals, and at doses of 4 and 8 mg/kg, induced variable changes in circulating levels of testosterone, elevated by the higher dose, and caused sperm suppression, in some animals to azoospermia. It was concluded that 8 mg/kg testosterone buciclate would provide adequate androgen replacement when combined with 4 mg/kg levonorgestrel butanoate as a putative male contraceptive regimen.

A non‐human primate study (baboon; Papio hamadryas) to determine if a long‐acting progestogen, levonorgestrel butanoate, combined with a long‐acting androgen, testosterone buciclate, can suppress spermatogenesis: II. Efficacy study

Two combined injections of levonorgestrel butanoate (4 mg/kg) and testosterone buciclate (8 mg/kg) at 3-month intervals to adult male baboons initiated a decrease in sperm concentration from baseline values of 490x10(6)/ml to minimum values of 17x10(6/ml. This suppression was sustained until week 32, during which time between one and three azoospermic samples were collected from each of four out of five treated baboons in the period 10-24 weeks. Circulating plasma levels of LH and testosterone decreased to approximately 20-75% of baseline values. Plasma levels of cortisol declined to significantly reduced levels at weeks 22 and 36-44. All values returned to the baseline range by week 48. The combined administration of progestogen and androgen induced a more marked and sustained suppression to severe oligozoospermia or azoospermia than did the equivalent dose of progestogen alone (Goncharov et al., 1995). Although the dose of testosterone buciclate used did not maintain peripheral levels of testosterone in the normal range, it did not restimulate spermatogenesis. It was concluded that a combination drug regimen based on the novel long-acting levonorgestrel and testosterone esters could provide a contraceptive option for men.

Which adult male savanna baboons form coalitions?

We investigated the mechanism of alliance formation among adult male savanna baboons by comparing the characteristics of males that formed coalitions frequently with males that never or seldom took part in coalitions. We observed three groups: two of Papio cynocephalus cynocephalusin Amboseli National Park, Kenya, and one of P. c. anubisin the vicinity of Gilgil, Kenya. We considered four hypotheses: (1) Males must be familiar with each other, (2) males must have an affinitive bond, (3) males must have more than average experience, and (4) the combined fighting ability of the coalition partners relative to the fighting ability of their opponent determines the likelihood that a coalition is formed. We conclude that relative fighting ability forms the key factor in coalition formation. High- ranking males do not form coalitions often, since they hardly need them. Low- ranking males rarefy form coalitions, since they cannot form effective coalitions among themselves. Affinity (“friendship”) may play a role as an additional factor. The relation of coalition formation with age and period of residence, which was found in several studies, can be explained largely by the correlation between these parameters and fighting ability.

Comparison of Skeletal Muscle Laser Doppler Flowmetry to Changes in Central Hemodynamics in Detecting the Physiological Response to Moderate Hemorrhage

Previous studies have demonstrated that laser Doppler (LD) flowmetry is a useful technique for following changes in blood flow in a tissue bed, but the potential role of LD flowmetry in management of the critically ill patient is unclear. This study sought to establish the sensitivity of LD flowmetry compared to changes in centrally measured hemodynamic parameters in response to a mild hemorrhagic episode. In order to establish the correlation between LD flow and actual blood flow, livers from Sprague-Dawley rats were isolated and perfused via the portal vein with citrate anticoagulated rat blood. Changes in LD flow were recorded while changing blood flow via the perfusion pump. There was a strong correlation between pump flow and LD flow (for N = 5 livers, r > 0.9; P < 0.05). This relationship was stable at hematocrits >20. The second part of this study tested the sensitivity of LD flowmetry in anesthesized baboons. An LD probe was placed on the surface of the gracilis muscle of the adult male baboons. LD flow and hemodynamic parameters were measured following two episodes of bleeding and reinfusing 250 cc of blood. During the first bleed there were significant changes in heart rate (97 + 8 to 159 + 12), mean arterial pressure (125 + 6 to 105 + 9), and LD flow (20.6 + 4.6 to 11.9 + 3.6); these parameters returned to normal after reinfusion of blood. During the second bleed, the only parameters that showed significant changes were heart rate (118 + 5 to 135 + 12) and LD flow (17.5 + 8 to 10.7 + 3.4). Cardiac output, pulmonary artery wedge pressure, and arterial blood pH by blood gas determination did not change significantly during either bleeding episode. This study suggests that LD flowmetry is more sensitive to tissue hypoperfusion than commonly measured central parameters and may be useful in aiding the resuscitation of critically ill patients.