Should the guidelines for monitoring serum cholesterol levels in the elderly be re-evaluated?

Elevated circulating cholesterol can have profound effects on the health of an individual. Such excess cholesterol can promote coronary artery disease, production and accumulation of β-amyloid in the brain, and possibly Alzheimer’s disease (AD). In a clinical trial evaluating the benefit of a cholesterol-lowering drug in the treatment of AD, mean cholesterol levels at baseline among individuals participating in the trial were found to be relatively high. Based on this observation we suggest that cholesterol levels should be actively monitored in the elderly, as many individuals with AD are over 65 years of age and therefore excluded by currently accepted guidelines.     

Evaluation of kangaroo pericardium as an alternative substitute for reconstructive cardiac surgery

BACKGROUND: Bioprosthetic materials (human, bovine and porcine) are used in various cardio-thoracic repair and replacement procedures because of excellent performance and low thrombogenicity. These bioprosthetic substitutes fail due to degeneration and calcification. This study examines the morphology, tensile properties and calcification potential of kangaroo pericardium in vitro and in vivo. METHODS: Bovine (control tissue) and kangaroo pericardium, fixed in 0.625% buffered glutaraldehyde, were examined by light and scanning electron microscopy. A standard method was used for biaxial testing. Pericardial strips (10 x 5 mm) were implanted subcutaneously into male Wistar rats and retrieved after 4, 6 and 8 weeks and examined by Von Kossa's stain technique and atomic absorption spectrophotometry. RESULTS: Histology revealed serosa and fibrosa cell layers in both tissues. Electron microscopy showed a densely arranged collagen matrix in kangaroo pericardium. Kangaroo pericardium calcified significantly less than bovine pericardium at 4 weeks (0.80+/-0.28 versus 21.60+/-4.80 microg/mg) at 6 weeks (0.48+/-0.08 versus 32.80+/-14.4 microg/mg) and at 8 weeks (2.40+/-1.20 versus 30.40+/-17.20 microg/mg), respectively. CONCLUSIONS: Kangaroo pericardium has a densely arranged collagen matrix with a higher extensibility and significantly lower calcification potential. Therefore, kangaroo pericardium could be used as an alternative substitute in cardiac surgery because of its low calcification potential.     

Human hematopoietic progenitors engraft in fetal canine recipients and expand with neonatal injection of fibroblasts expressing human hematopoietic cytokines

OBJECTIVE: The development of large-animal models for human hematopoiesis will facilitate the study of human hematopoietic stem cells and their progenitors in vivo. In previous studies, human hematopoietic progenitors engrafted in fetal dogs and contributed to hematopoiesis for one year. Despite initially high levels of human cells, the proportion declined to less than 0.1% at 6 months, possibly due to inability of the canine hematopoietic microenvironment to support ongoing human hematopoiesis. In the current experiments we examined the potential of co-transplanting fibroblasts expressing human hematopoietic cytokines with the hematopoietic graft to increase the contribution of human progenitors to chimeric hematopoiesis. METHODS: Mid-gestation canine fetuses were injected with 1-3 x 10(7) human cord blood cells and 1 x 10(7) murine fibroblasts engineered to express human cytokines. Neonatal pups were boosted with additional injections of cytokine-expressing fibroblasts. Human cell engraftment was monitored by PCR amplification of human-specific DNA sequences from recipient hematopoietic tissues. RESULTS: Human hematopoietic cells were detected in 13/15 fetal recipients for at least 7 months. At time points up to 30 weeks of age, human DNA was detected in stimulated lymphocyte cultures, approximately 0.1% of blood leukocytes and 1.5% (85/5757) of myeloid colonies. Eight months postinfusion, 1.7% of colony-forming units (CFUs) were of human origin. By one year 0.5% or less of myeloid colonies and less than 0.01% of blood leukocytes carried human DNA. Following an infusion of cytokine-expressing fibroblasts at one year, the proportion of human myeloid progenitors rose to 11.5% and remained detectable for 8 months. CONCLUSION: These studies confirm that human hematopoietic progenitors can engraft in fetal pups and contribute to multilineage hematopoiesis. Infusion of cells expressing human cytokines is one approach to stimulate human hematopoietic progenitors in vivo and thus increase their contributions to chimeric hematopoiesis.     

Whole body protein metabolism in children with cancer

Whole body protein synthesis and catabolism were measured using the [ring-2H5]phenylalanine and [1-13C]leucine primed constant infusion technique in 32 paediatric patients with cancer at different stages of treatment. Rates of synthesis (S) and catabolism (C) derived from the [ring-2H5]phenylalanine and [1-13C]leucine models were 4.7 (SD 1.3) (S) and 6.0 (1.5) (C) g/d/kg, and 5.5 (0.8) (S) and 6.8 (1.2) (C) g/d/kg, respectively. These results show that these two tracer techniques give similar results in this study population. Comparison of these values with results previously reported for groups of control children using the [ring-2H5]phenylalanine model (S = 3.69 and 3.93; C = 4.09 and 4.28 g/d/kg) and the [1-13C]leucine model (S = 4.32; C = 4.85 g/d/kg) show that rates of synthesis and catabolism were higher in cancer patients than in controls. Thus whole body protein turnover is increased in children under treatment for cancer. Other indices of metabolism such as plasma amino acids and intermediary metabolites were also measured and showed that, although subjects were in isotopic steady state, there were significant metabolic changes during the course of the primed constant infusions used to measure protein turnover.     

Rotator cuff tear: clinical experience with sonographic detection

Between June 1986 and April 1988, 86 sonographic examinations of the shoulder were performed on patients suspected of having rotator cuff tears. Major sonographic diagnostic criteria included (a) a well-defined discontinuity usually visible as a hypoechoic focus within the cuff, (b) nonvisualization of the cuff and (c) an echogenic focus within the cuff. Seventy-five patients underwent both sonography and arthrography. Compared with arthrography alone, ultrasound examinations enabled detection of 92% of rotator cuff tears (24 of 26 tears), with a specificity of 84% and a negative predictive value of 95%. Correlation was obtained in 30 of these patients who underwent surgery for rotator cuff tear or other soft-tissue abnormality. In this group, the sensitivity of sonography for detection of a tear was 93%, with a specificity of 73%, while for arthrography sensitivity was 87% and specificity was 100%. These data indicate that sonography is a useful, noninvasive screening procedure for patients suspected of having rotator cuff injury.     

Absence of 5-HT3 and cholinergic mechanisms in improgan antinociception

Improgan, an analgesic derived from histamine antagonists, acts in the brain stem to activate descending non-opioid, pain-relieving circuits, but the mechanism of action of this drug remains elusive. Because improgan has a moderate affinity for 5-HT(3) receptors, and, since cholinergic and serotonergic drugs can modulate descending analgesic circuits, roles for 5-HT(3), nicotinic and muscarinic receptors in improgan antinociception were presently investigated in rats. Improgan (80 microg, icv) induced nearly maximal inhibition of hot plate and tail flick nociceptive responses, and these actions we unaffected by antagonists of muscarinic (atropine, 5.9 mg/kg, i.p.) and nicotinic (mecamylamine, 2 mg/kg, i.p.) receptors. Control experiments verified that these antagonist treatments were maximally effective against muscarinic and nicotinic antinociception in both tests. In addition, improgan antinociception was unaffected by icv pretreatment with a 5-HT(3) antagonist (ondansetron, 20 microg). When given alone, icv treatment with neither this antagonist nor a 5-HT(3) agonist (m-chlorophenylbiguanide, 1000 nmol, icv) modified thermal nociceptive latencies. These results show no role for supraspinal cholinergic and 5-HT(3) receptors in improgan antinociception. The findings help to narrow the search for the relevant mediators of the action of this novel analgesic agent.