LONG-TERM OUABAIN ADMINISTRATION DOES NOT ALTER BLOOD PRESSURE IN CONSCIOUS SPRAGUE-DAWLEY RATS

1. We tested the ability of ouabain to cause chronic hyper tension by continuously infusing ouabain for 28 days (mini-osmotic pump implantation; i.p.). The blood pressure and metabolic effects of sham (150 mmol/L NaCI; n= 12) or ouabain infusion (10 μg/kg per day; n= 14; 100 μg/kg per day; n = 14) were examined in conscious Sprague-Dawley rats. 2. Plasma ouabain concentrations measured after 28 days of ouabain infusion were as follows: sham, not detectable (n= 11); ouabain 10 μg/kg per day, 0.60 ± 0.07 nmol/L (n= 14); and ouabain 100 μg/kg per day, 7.17 ± 0.57 nmol/L (n= 14; P < 0.001). 3. Sham or ouabain infusion did not alter food intake, bodyweight, water intake or urine output in conscious rats. 4. Blood pressure was not altered by sham treatment. Ouabain at 10 μg/kg per day or 100 μg/kg per day did not produce consistent rises in blood pressure. Ouabain at 10 μg/kg per day increased blood pressure on treatment day 12 only (+ 6mmHg; P < 0.05), while at 100μg/kg per day blood pres sure increased on treatment days 16 (+ 9 mmHg; P < 0.05) and day 18 (+ 8mmHg; P < 0.05) only. There was no significant difference in blood pressure between sham and ouabain groups. 5. Renal blood flow was decreased in rats infused with ouabain at 10 μg/kg per day (2.0 ± 0.3 mL/min per 100 g body-weight; n= 5; P < 0.01) and 100 μg/kg per day (2.2 ± 0.4 mL/ min per 100 g bodyweight; n= 7; P < 0.05) compared with sham treatment (3.5 ± 0.2 mL/min per 100 g bodyweight; n= 6). Renal vascular resistance was increased in rats treated with ouabain at 10 μg/kg per day (65.5 ± 12.6 mmHg/mL per min per 100 g bodyweight; n= 5; P < 0.01) and 100 μg/kg per day (66.0 ± 15.6 mmHg/mL per min per 100 g bodyweight; n= 7; P < 0.05) compared with sham treatment (32.6 ± 2.5 mmHg/mL per min per 100 g bodyweight; n= 6). 6. High plasma concentrations of ouabain do not cause consistent increases in blood pressure in conscious Sprague-Dawley rats.     

Object recognition versus object discrimination: comparison between human infants and infant monkeys.

Human infants (12-32 months old) and adults learned a delayed nonmatching-to-sample (DNMS) task and single- and multiple-pair discrimination tasks using nonverbal procedures previously used with monkeys. Infants learned discriminations rapidly and at a young age (12 months), but they required prolonged training and maturation before learning the DNMS task. Adults learned all tasks rapidly. After learning the DNMS task to criterion, memory performance declined systematically in an inverse relation to age. The dissociation in ability of infants on the DNMS versus discrimination tasks closely resembles the dissociation previously reported with infant monkeys (Bachevalier & Mishkin, 1984). Results from both infant humans and monkeys support a neurocognitive maturational model.     

Use of long catheters for multipatient anesthetic monitoring at high respiratory frequencies

Anesthetic gases from several patients can be monitored simultaneously with a centrally located mass spectrometer. Such monitoring requires catheters from patient to spectrometer that are several meters long. Scamman (J Clin Monit 1988;4:227–229) found that when the respiratory frequency is high, as with infants, the CO₂ signal from the patient is unacceptably distorted during passage down the catheter. This is due to Taylor dispersion of the input signal. An outline of the theory of Taylor dispersion is given. The equations describe the interaction between the velocity distribution (which, in laminar flow, is parabolic) and the radial diffusion of CO₂. This interaction keeps a tracer signal together in a pulse, as it moves down the tube with themean velocity, spreading somewhat as it proceeds. How much does an initially sharp signal become blurred? The spread of such a signal when it reaches the detector, measured in time, can be expressed in various ways. Measurement is complicated, however, by the fact that the gas pressure may fall by as much as a factor of 10 along the line. The resultant expansion and acceleration of the gas cannot be ignored. A full treatment of this complication is given elsewhere, but the following simple equation is described: {ie237-1} Typically, the spread time is up to a quarter of a second for catheters of 50 m, such as used by Scamman. This is comparable with the period of CO₂ rise and fall for infants and explains the serious distortion in wave form that Scamman found. Some distortion can be eliminated by reducing R to 0.1 or less, but the extent of this improvement is small. Ideally, for fast-breathing patients, the catheter length should be reduced to 20 m or less, if possible.     

Efficacy of autograft and freeze-dried allograft to enhance fixation of porous coated implants in the presence of interface gaps.

Autogenous cancellous bone and freeze-dried allogeneic cancellous bone were tested in a total of 41 adult male mongrel dogs. In each humerus, an implant with a commercially pure titanium fiber metal porous coating was placed in an overreamed cavity so that a uniform 3-mm gap was present between the implant and host cancellous bone. Graft material was placed in the gap of one humerus while the gap of the other humerus was left empty and served as a paired negative control. Histologically, both autograft and allograft appeared to aid repair of the defect, but quantitatively only autograft enhanced new bone formation within the defect. Treatment with autograft significantly increased the amount of bone ingrowth within the implants by nearly three-fold at 4 weeks and eight-fold at 8 weeks. The enhancing effect was recognizable as early as 2 weeks. The strength of fixation was increased by nearly seven-fold at 4 weeks and two-fold at 8 weeks in the autograft group, but this was only statistically significant at 4 weeks. Treatment with allograft did not enhance bone ingrowth at any time period, but had a small positive effect on strength of fixation at 4 weeks.     

Periosteal remodeling at the femoral neck in nonhuman primates.

Periosteal bone turnover is poorly understood. We documented intramembranous periosteal bone turnover in the femoral neck in intact nonhuman primates and an increase in osteoclast numbers at the periosteal surface in sex steroid-deficient animals. Our studies are the first to systematically document periosteal turnover at the femoral neck. INTRODUCTION: Bone size is an important determinant of bone strength, and cellular events at the periosteal surface could alter bone dimensions. We characterized periosteal cellular activity with dynamic histomorphometric studies of nonhuman primate femoral neck and shaft. MATERIALS AND METHODS: Femur specimens from 16 intact adult male and female nonhuman primates (Rhesus [Macaca mulatta, n = 9] and Japanese Macaque [Macaca fuscata, n = 7]) were analyzed. Animals were double-labeled with tetracycline, and necropsy was performed 2-7 days after the last dose. We characterized periosteal resorptive activity in an additional group of five intact and four castrate female animals. Multiple group comparisons in intact animals were performed by one-way ANOVA followed by a Fisher PLSD posthoc test. In gonadectomized animals, Fisher's exact test was used for dichotomous and Mann-Whitney U-test for continuous variables. RESULTS: Bone turnover in the periosteum of the femoral neck in intact animals was more rapid than at the femoral shaft but slower than in femoral neck cancellous bone. Similarly, in these intact animals, the eroded surface of cortical bone at the femoral neck periosteal surface was significantly greater than in the cancellous bone compartment (p < 0.0001) or on the femoral shaft (p < 0.0001). Gonadectomized female animals showed an increase in osteoclast number on the periosteal surface compared with intact controls (p < 0.01). CONCLUSIONS: We documented intramembranous periosteal bone turnover in the femoral neck by histomorphometric analyses. The tissue level bone formation rate was sufficient to add substantively to femoral neck size over time. Periosteal osteoclastic activity was not the result of the emergence of intracortical tunneling at the bone surface. Sex steroid deficiency produced an increase in osteoclast numbers at the periosteal surface. This is the first systematic documentation of periosteal turnover at the femoral neck.     

A diagnostic algorithm for male genital oedema

Male genital oedema can be defined as swelling or the appearance of swelling of the scrotum and/or the penile shaft and prepuce. Despite the various causes of genital oedema reported in the published work, a concise approach to the evaluation and management has not been sufficiently addressed.     

Flow Cytometric Analysis of Cellular Changes in Mice after Intradermal Inoculation with a Liposome–Iscom Adjuvanted Vaccine

As it is not known what changes to leucocyte homeostasis are mandatory for effective adjuvant action, the biological relevance of systemic changes elicited by different vaccine formulations can only be interpreted in the context of the immunological outcomes. We used flow cytometry to quantify the changes in leucocyte subsets induced in mice intradermally immunized with SAMA4 (adjuvant group), outer membrane proteins (OMP) purified from Actinobacillus pleuropneumoniae (OMP antigen group), SAMA4 adjuvanted OMP (OMP vaccine group), or phosphate-buffered saline (PBS: control group). This approach allowed direct comparisons to be made between the effects of antigen, adjuvant or antigen–adjuvant complexes on immune effector cell populations. Antigens complexed with the liposome–iscom hybrid adjuvant, SAMA4, generated strong antibody responses and cytotoxic T-cell activity in animals immunized intradermally, reflecting remobilization and recruitment of specific cell populations. Splenomegaly, due to granulocytosis, monocytosis and megakaryocytosis, was most prominent in the OMP vaccine group. Histological examination of spleen sections confirmed that these changes were due primarily to splenic haematopoiesis. Circulating numbers of granulocytes and monocytes increased significantly (P < 0.05) in the blood of the OMP vaccine group, as did granulocyte numbers in the lungs (P < 0.05). No changes in T- and B-cell numbers were detected by flow cytometry in the spleens, lungs or blood over the 28-day period in any treatment group. Thymocyte numbers (predominantly CD4⁺CD8⁺ cells) in the OMP vaccine group fell by 95% within 3 days of immunization. Identical cellular responses were obtained when an innocuous antigen, ovalbumin, was complexed with SAMA4 instead of OMP, thus demonstrating that the adjuvant effects of SAMA4 were due to synergistic interaction between antigen and adjuvant and not due to the presence of toxic components. The association of strong adaptive immune responses with such complex changes in leucocyte homeostasis induced by complexing adjuvant and antigen suggested that the changes were important for effective vaccination and were not purely circumstantial.