Postexposure chemoprophylaxis with ZDV or ZDV combined with interferon-alpha: failure after inoculating rhesus monkeys with a high dose of SIV.

Presently, no information is available regarding the efficacy of chemoprophylaxis in controlled human trials following accidental exposure to the human immunodeficiency virus (HIV). Using the closely related simian immunodeficiency virus (SIV) in rhesus monkeys, which develop a disease closely resembling human AIDS, we tested the efficacy of either single-agent 3'-azido-3'-deoxythymidine (ZDV) or the combination of ZDV plus recombinant human interferon-alpha (IFN-alpha). Treatment was started 3 h following inoculation of a high dose of SIV and continued for 21 days. SIV-inoculated control animals remained untreated. Virus was recovered from all monkeys on day 8, and by week 7 all had seroconverted. In contrast to monkeys treated with ZDV alone, animals given combination therapy had lower levels of p27 gag antigen compared to untreated controls on day 8 (p = 0.043). We conclude that neither treatment regimen could prevent infection after high-dose virus exposure; however, combination therapy may have depressed the level of virus replication more effectively than ZDV alone.

An investigation of a compliant interface for press-fit joint replacement.

Earlier in vitro studies showed that a compliant layer between a metal surface and trabecular bone improved the load distribution. In this study, the behavior of a compliant layer of Dacron velour was investigated in vivo using a patella resurfacing in a sheep as a model. Bilateral cases were used to compare the velour interface with a direct metal-to-bone interface. For the metal patellas, a fibrous layer developed adjacent to the metal while the underlying bone formed a new subchondral-like layer. With the velour interface, fibrous tissue invaded the velour, followed later by bone, which sometimes reached the metal surface. For follow-ups of 8 months or more, the load across the interface was transferred over localised patches, for both the press-fit and velour interfaces. There was no significant difference in the areas of contact. There was evidence that this was due to the irregularity of the bony surface beneath the fibrous layer, or to bone nodules actually growing up to the metal. It was concluded that in this in vivo model, the velour layer did not retain a more uniform load distribution compared with the press-fit joint, due to the nature of the bone and fibrous tissue that formed at the interfaces.

Characterization of inheritance patterns of blood pressure in Macaca fascicularis.

A breeding colony of Macaca fascicularis was established at the New England Regional Primate Center in 1977 and continued through 1984. Characterization of the offspring of this colony at 18 and 30 months of age suggested that higher blood pressure levels are hereditary in M. fascicularis, but evidence to date cannot determine if this condition is harmful to the animals.

Effect of dietary fat saturation on plasma lipoproteins and high density lipoprotein metabolism of the rhesus monkey.

Rhesus monkeys were fed corn or coconut oil-based diets for 3-6 mo to determine effects on the composition of all lipoprotein classes and on the metabolism of high density lipoproteins (HDL). Major findings included the following. Coconut oil feeding increased concentrations of all classes of plasma lipoproteins without altering lipoprotein size, suggesting an increase in particle number. The percentage of saturated fatty acids in the cholesteryl esters (CE) of low density lipoproteins (LDL) and HDL reached 40% with coconut oil feeding. This value probably constitutes a minimum estimate of the CE which were of intracellular rather than intraplasmic origin. The CE in LDL and HDL were nearly identical suggesting virtually complete equilibration by the core lipid transfer reaction. The CE in very low density lipoproteins, in contrast, were significantly more saturated than those in LDL and HDL irrespective of diet. Lower HDL levels on the corn oil diet were associated with higher fractional catabolic rates for both apolipoprotein A-I (0.42 vs. 0.31 d-1) and apolipoprotein A-II (0.45 vs. 0.30 d-1).

Autonomic nervous system activity in Macaca fascicularis.

This study was performed to determine the contributions of the sympathetic and parasympathetic nervous systems to cardiovascular control. Hexamethonium was administered to block the autonomic ganglia, propranolol to block beta adrenergic receptors of the sympathetic nervous system, and methylatropine to block the parasympathetic nervous system. The results of this study indicate high sympathetic tone and low parasympathetic tone in resting Macaca fascicularis. These findings are different from those in man but are similar to other nonhuman primates.

Enhanced blood pressure responses to loud noise in offspring of monkeys with high blood pressure.

Sixteen unanesthetized immature Macaca fascicularis monkeys, 18-43 months of age, were tested for mean arterial blood pressure (MBP) and heart rate (HR) responses to 30 minutes of continuous broadband noise (95 dB). Eight animals (OH group) were offspring of monkeys with high blood pressure (parents' MBP = 115.5 +/- 1.0 (SEM) mmHg), and eight (OC group) were offspring of control animals with normal blood pressure (parents' MBP = 96.6 +/- 1.7 mmHg). Resting MBP during a 17-24 hour period prior to the experiment in the OH group was 100.6 +/- 1.9 mmHg, significantly higher (p less than 0.05) than the MBP of the OC group (94.3 +/- 2.2 mmHg.) Immediately prior to noise exposure, MBP in the OH group was stable for 30 minutes, at 104 +/- 3 mmHg. During noise exposure, MBP increased significantly to 108 +/- 4 mmHg. In the OC group, MBP during the 30 min baseline interval was 95 +/- 2 mmHg, and during noise exposure was not significantly changed at 94 +/- 3 mmHg. Heart rate decreased significantly during noise in the OC group and did not change in the OH group. The results indicate that the offspring of monkeys with high blood pressure had higher resting MBP than control animals and showed significant MBP increases in response to loud noise. Control animals showed no change in MBP and decreases in HR in response to noise.

Approaches to the interface problem in total joint arthroplasty.

Bone shape and composition and the configurations and interface conditions of implant components influence the stability of the joint in various ways. A stable interface depends on overall stress and microstress distribution on the bone, particularly trabecular bone. Pressure pattern studies illustrated the effect of tibial component design on overall pressure distribution. Experiments in knee joints of sheep showed that a velour layer interposed between a metallic implant and bone induces fibrous ingrowth. It was proposed that this situation could reduce peak microstresses in trabecular bone.

Acute hypertension in a nonhuman primate: humoral and hemodynamic mechanisms.

The present study assessed the contribution of the renin-angiotensin system (RAS), dietary sodium, and cardiac output (CO) to the genesis of primate hypertensin in a one-kidney model which was developed to test species-specific renin inhibitors. Reduction of renal perfusion pressure increased mean arterial pressure (MAP) from 105 +/- 4 to 127 +/- 3 mm Hg (p less than 0.0005), associated with increased plasma renin activity (PRA) from 4.9 +/- 0.7 to 13.8 +/- 1.1 ng. ml-1.hr-1 (p less than 0.0005). Correlation of MAP with PRA yielded an r value of 0.662 (p less than 0.0005). Significant blood pressure elevation was obtained with both regular (R) and low sodium (LS) diet (p less than 0.0005), although the MAP change was greater with LS. With both R and LS diet, hypertension was associated with increased PRA (p less than 0.0005), and normotensive pressures were achieved with converting enzyme inhibitor (teprotide). The hemodynamic change with hypertension was an increase of systemic vascular resistance (SVR) from 0.89 +/- 0.12 to 1.17 +/- 0.09 units (p less than 0.05); cardiac output (CO) and central blood volume did not change significantly. Thus, acute hypertension, mediated by the RAS, was developed in a one-kidney primate model. The hemodynamic correlate of hypertension was increased SVR; CO and volume redistribution were not initiating factors.

Noma in a nonhuman primate.

A lesion in Macaca cyclopis which appears to conform to defined characteristics of noma in human beings has been reported. Clinical features in common include the gangrenous appearance of the lesion, the association with necrotizing ulcerative gingivitis, and the massive destruction of soft tissue and bone in the oronasofacial regions. Systemic features in common include debilitation of the host, leukocytosis, and depression of cellular immunologic responses. Microbiologic studies revealed the presence of organisms commonly found in necrotizing ulcerative gingivitis. The detection of true noma in nonhuman primates may now allow the opportunity for study of the etiology, pathophysiology, and therapy of this condition for human benefit.

Protein-losing enteropathy in six macaques.

Using intravenous administration of radioactive labeled chromic chloride, which binds to plasma proteins, protein-losing enteropathy was documented in 6 macaques (Macaca mulatta and Macaca arctoides) with progressive weight loss and hypoalbuminemia. Four clinically normal macaques lost 0.5% +/- 0.1% of the label in feces over 4 days, compared with the diseased macaques, which lost from 1.0%--14.2% of the dose during the same period. Lesions in the small intestine (lymphangiectasia, amyloidosis of lamina propria, mast cell proliferation in the tunica muscularis and submucosa, and goblet cell hyperplasia) were associated with the protein-losing enteropathy.