The human knee meniscus: a review with special focus on the collagen meniscal implant

The human knee meniscus is important for the protection of the knee joint from degeneration. Because it is so commonly injured, several methods have been developed to replace damaged meniscal tissue with either transplanted menisci or other synthetic implants. Here we review these different approaches, with a clinical and histological focus on the collagen meniscal implant (CMI or Menaflex), a tissue-engineered bovine collagen product. Clinical trials in patients receiving the CMI have demonstrated good clinical outcomes in follow-ups as long as 10 years. We review the findings of second-look biopsies of implanted CMI constructs; they demonstrate the fibrochondrocytic ingrowth of tissue mimicking a native meniscus. Integration of the CMI to host meniscus is also confirmed. The histologic inflammation occasionally observed around the graft appears to be of little clinical significance. We conclude that tissue-engineered menisci from bovine collagen are safe in the time period examined and that they hold promise for future repair of the meniscus in appropriate individuals.     

In Vitro Antimycobacterial Activities of 2′-Monosubstituted Isonicotinohydrazides and Their Cyanoborane Adducts

As a result of our search for new isoniazid derivatives with extended spectra of activity, we evaluated the in vitro antimycobacterial activities of isonicotinohydrazides (compounds 2) and their cyanoborane adducts (compounds 3), both obtained by the reaction of isonicotinoylhydrazones (compounds 1) with sodium cyanoborohydride. Most of the tested compounds displayed moderate to high activity against Mycobacterium tuberculosis H37Rv, with MICs ranging from 0.2 to 12.5 microg/ml. In particular, some hydrazides showed activity similar to that of rifampin (MIC = 0.2 microg/ml) and rather low cytotoxicity, so that they were generally shown to possess high safety indices. In contrast, the coordination to a cyanoborane (BH(2)CN) group (compounds 3) in general brought about a decrease in antimycobacterial activity, while cytotoxicity increased. Interestingly, selected compounds 1 to 3, mostly hydrazides (compounds 2), were effective in killing M. tuberculosis growing within macrophages at concentrations in culture medium which were much lower than the corresponding MICs. These compounds also displayed good activity against drug-resistant M. tuberculosis strains.     

Oxygen-derived free radicals and postischemic myocardial reperfusion: therapeutic implications

Oxygen-derived free radicals have been implicated in the pathogenesis of various disease states, including myocardial ischemia and reperfusion. In this article, we review 1) the evidence linking free radical production and myocardial injury during myocardial ischemia and reperfusion and 2) results of studies of the effects of the pharmacological therapies available potentially to prevent free radical-mediated injury. Free radicals can be produced during ischemia and reperfusion by several different biochemical pathways. Of these, the xanthine oxidase reaction and the output of free radicals by neutrophils that have accumulated in damaged tissue have been studied extensively. When produced, free radicals can potentially damage myocytes or endothelial cells through peroxidation of membrane lipids or damage to proteins or nucleic acids. Using electron spin resonance spectroscopy, several studies have shown a 'burst' of oxygen free radicals immediately after reperfusion. Moreover, exogenous generation of intravascular free radicals has been shown to produce marked vascular and myocyte damage, as well as contractile dysfunction. 'Anti-free radical' interventions, such as xanthine oxidase inhibitors and free radical scavengers have been reported to prevent contractile dysfunction and reperfusion-induced arrhythmias after an episode of reversible ischemic injury. However, after more severe episodes of ischemia, such interventions have had conflicting effects on myocardial infarct size. 'Anti-free radical' interventions could be of potential use in situations where reversible ischemic injury occurs. In situations where reperfusion is achieved after irreversible ischemic injury has occurred, the potential beneficial effect of these treatments on infarct size is more doubtful.     

Effects of propranolol on bone metabolism in the rat

Propranolol, a nonspecific beta-blocker has many physiologic effects. Its effects on bone in vivo are unknown, although beta receptor sites have been found on osteoblasts. In this study, the hypothesis tested was that low doses of propranolol could alter bone properties and enhance orthotopic endochondral bone formation. In a group of nonsurgical rats, propranolol treatment increased femoral torsional strength on biomechanical testing. In the rat surgical model used, right femora were fixed to a polyethylene plate and then defects were created mid-diaphysis and subsequently filled with demineralized bone matrix. These rats (defect rats) were randomly divided into groups that were given propranolol or a saline carrier for 19 consecutive days. In the defect rats, increased trabecular femoral metaphyseal mineral apposition rates were observed in propranolol-treated groups. Densitometry and roentgenographic scoring of callus formation after 12 weeks in propranolol-treated rats revealed increased callus and bone union. The results of this study indicate that propranolol treatment can significantly affect bone properties.     

Intravascular signal in MR imaging: use of phase display for differentiation of blood-flow signal from intraluminal disease

Intravascular signal from flowing blood is frequently observed on magnetic resonance (MR) images and may be indistinguishable from partial or complete vascular occlusion caused by thrombus or tumor. With a phase-display reconstruction method, qualitative assessment of large-vessel patency within the abdomen was undertaken in 15 healthy subjects and 12 patients with angiographically or surgically documented intravascular thrombus or tumor. Computed tomographic (CT) scans were available in all patients for correlation. MR studies were performed with a multisection spin-echo pulse sequence and two-dimensional Fourier transform spatial encoding. Data acquired from a single sequence was reconstituted in two ways to provide both routine anatomic images and a pictorial representation of large-vessel flow on a phase-sensitive image. With this method, reliable and easy differentiation of intraluminal thrombus and tumor from blood flow signal within large vessels was achieved. Information from these phase-display images compared favorably with findings from angiography and contrast-enhanced CT in the determination of luminal patency and obstruction.     

Bone disease in prolonged parenteral nutrition: osteopenia without mineralization defect

A metabolic bone disease characterized by a mineralization defect, low plasma 1,25(OH)2D, and hypercalciuria has been described in patients receiving prolonged total parenteral nutrition (TPN). Because the practice of TPN differs from center to center, we investigated 13 home TPN patients to determine whether they had similar or different bone abnormalities. They had received TPN for a mean period of 51 +/- 38 mo. Bone pain occurred in six patients and two had multiple vertebral and rib fractures (with trauma in one patient). Bone pain was mild to moderate and not incapacitating. Bone histomorphometry showed reduced bone volume, reduced osteoid with normal resorption and calcification rates. These abnormalities were associated with hypercalciuria, but the plasma levels of 1,25(OH)2D were normal. Abnormalities in bone metabolism in this group of patients suggest a fundamental decrease in bone matrix-formation rather than a mineralization defect as the underlying mechanism.