Video-assisted lateral intertransverse process arthrodesis. Validation of a new minimally invasive lumbar spinal fusion technique in the rabbit and nonhuman primate (rhesus) models

STUDY DESIGN: Cadaveric anatomic and in vivo survival animal studies were performed to develop a new arthrodesis technique for the lumbar spine. OBJECTIVES: To examine the feasibility, efficacy, and safety of a minimally invasive lumbar intertransverse process arthrodesis technique using an osteoinductive growth factor (rhBMP-2) delivered in a collagen sponge carrier. The technique was first developed using a rabbit model and modified for the nonhuman primate (rhesus monkey), a larger animal with the most similar bone biology to humans. SUMMARY OF BACKGROUND DATA: The morbidity of conventional posterolateral lumbar intertransverse process arthrodesis includes graft donor site morbidity; paraspinal muscle devascularization, denervation, and scarring and nonunion in up to 36% of patients. Minimally invasive anterior lumbar interbody arthrodesis techniques have been developed, but these often require a metal implant and carry risks to major vessels and development of retrograde ejaculation. A minimally invasive technique for posterolateral intertransverse process arthrodesis has not been described previously. METHODS: In Part 1, we examined seven New Zealand white rabbits and five rhesus monkeys at necropsy and during nonsurvival surgeries to determine the best access routes and to develop special instruments for video-assisted lateral intertransverse process arthrodesis. In Part 2, 38 New Zealand white rabbits underwent L4-L5 intertransverse process arthrodesis: the "OPEN" group (n = 16) underwent a standard open muscle-splitting approach using rhBMP-2 (bone morphogenetic protein) and collagen as a bone graft substitute; the "video-assisted control" group (n = 6) underwent video-assisted lateral intertransverse process arthrodesis with the collagen implant only (no growth factor); and the "video-assisted-BMP" group (n = 16) underwent video-assisted lateral intertransverse process arthrodesis with rhBMP-2 and collagen as the graft material. In Part 3, rhesus monkeys (n = 4) underwent video-assisted lateral intertransverse process arthrodesis using rhBMP-2 and collagen after laminectomy of L4-L5. RESULTS: In Part 1, we identified expedient, minimally invasive routes to the intertransverse process interval appropriate for each species: an intermuscular approach for the rabbit and a lateral, extramuscular approach for the rhesus monkey. In Part 2, all rabbits in the OPEN and video-assisted-BMP groups achieved solid intertransverse process lumbar fusions when assessed at 10 weeks. There were no neurologic impairments nor any difference between the two groups in the frequency of postoperative infection or other complications. None of the animals in the video-assisted control group showed evidence of fusion. In Part 3, exposure, decortication and grafting with rh-BMP-2 and collagen was accomplished successfully in all four monkeys through the video-assisted minimally invasive approach without complications. CONCLUSION: Video-assisted lateral intertransverse process arthrodesis is a feasible, effective, and safe method of lumbar spinal fusion in the rabbit and rhesus monkey. Use of this arthrodesis procedure will minimize the morbidity of paraspinal muscle denervation and devascularization seen with open intertransverse process fusion techniques, and the use of an osteoinductive growth factor will eliminate the problem of graft donor site morbidity and possibly increase the chances for successful fusion.     

Role of ERAB/L-3-hydroxyacyl-coenzyme A dehydrogenase type II activity in Abeta-induced cytotoxicity

Endoplasmic reticulum-associated amyloid beta-peptide (Abeta)-binding protein (ERAB)/L-3-hydroxyacyl-CoA dehydrogenase type II (HADH II) is expressed at high levels in Alzheimer's disease (AD)-affected brain, binds Abeta, and contributes to Abeta-induced cytotoxicity. Purified recombinant ERAB/HADH II catalyzed the NADH-dependent reduction of S-acetoacetyl-CoA with a Km of approximately 68 microM and a Vmax of approximately 430 micromol/min/mg. The contribution of ERAB/HADH II enzymatic activity to Abeta-mediated cellular dysfunction was studied by site-directed mutagenesis in the catalytic domain (Y168G/K172G). Although COS cells cotransfected to overexpress wild-type ERAB/HADH II and variant beta-amyloid precursor protein (betaAPP(V717G)) showed DNA fragmentation, cotransfection with Y168G/K172G-altered ERAB and betaAPP(V717G) was without effect. We thus asked whether the enzyme might recognize alcohol substrates of which the aldehyde products could be cytotoxic; ERAB/HADH II catalyzed oxidation of a variety of simple alcohols (C2-C10) to their respective aldehydes in the presence of NAD+ and NAD-dependent oxidation of 17beta-estradiol. Addition of micromolar levels of synthetic Abeta(1-40) to purified ERAB/HADH II inhibited, in parallel, reduction of S-acetoacetyl-CoA (Ki approximately 1.6 microM), as well as oxidation of 17beta-estradiol (Ki approximately 3.2 microM) and (-)-2-octanol (Ki approximately 2.6 microM). Because micromolar levels of Abeta were required to inhibit ERAB/HADH II activity, whereas Abeta binding to ERAB/HADH II occurred at much lower concentrations (Km approximately 40-70 nM), the latter more closely simulating Abeta levels within cells, Abeta perturbation of ERAB/HADH II was likely to result from mechanisms other than the direct modulation of enzymatic activity. Cells cotransfected to overexpress ERAB/HADH II and betaAPP(V717G) generated malondialdehyde-protein and 4-hydroxynonenal-protein epitopes, which were detectable only at the lowest levels in cells overexpressing either ERAB/HADH II or betaAPP(V717G) alone. Generation of such toxic aldehydes was not observed in cells contransfected to overexpress Y168G/K172G-altered ERAB and betaAPP(V717G). We conclude that the generalized alcohol dehydrogenase activity of ERAB/HADH II is central to the cytotoxicity observed in an Abeta-rich environment.     

Effect of cholesterol and cholestyramine feeding and of fasting on sterol synthesis in the liver, lleum, and lung of the guinea pig

The effects of feeding diest containing either cholesterol (0.24% w/w) or cholestyramine (2.5% w/w) and of fasting on sterol synthesis in the liver, ileum, and lung of both male and female guinea pigs have been studied by measuring the incorporation by tissue slices of 14C-labeled acetate into total digitoninpredipitable sterols. Cholesterol feeding significantly decreased (P less than 0.05) sterol synthesis in the liver, ileum, and lung of the males and in the ileum of females. Cholestyramine feeding stimulated the rate of hepatic sterol synthesis 13-fold but did not significantly affect sterologenesis in the ileum. Sterol synthesis in the lung was significantly increased (P less than 0.05) but to a much lesser extent than in the liver. Fatty acid synthesis in the liver, ileum, and lung was not significantly affected by either cholesterol or cholestyramine feeding. In guinea pigs fasted for 24 hr, sterol synthesis was inhibited in all three tissues, the most pronounced effect occurring in the liver. Only in the lung was fatty acid synthesis significantly decreased (P less than 0.001) by fasting. Cholesterol feeding resulted in increased concentrations of cholesterol in the plasma and liver. Cholestyramine feeding reduced plasma cholesterol concentration by 81% in females and by 64% in males. However, it did not significantly change the tissue cholesterol concentrations. Fasting resulted in a significant increase (P less than 0.05) in plasma cholesterol concentration but did not effect the concentration of cholesterol in the tissues. It was concluded that in the normal guinea pig, the feedback inhibition produced by both cholesterol and also possibly by bile acids suppresses sterol synthesis in the liver to very low rates compared to those in the small intestine, where sterologenesis is not only less sensitive to the cholesterol negative feedback system than that in the liver, but also is not subject to regulation by the bile acid negative feedback system.     

Production of tubular structures from the aerial mycelium of Actinomyces roseoflavus var. roseofungini]

Jejunal lamina propria plasma cells and eosinophils and intraepithelial lymphocytes were raised in coeliac children on gluten-containing diets, but only intraepithelial lymphocytes were increased in patients on gluten-free diets. In contrast, lamina propria lymphocytes were reduced in children with coeliad disease on gluten-containing diets but were normal in paitents on gluten-free diets. In children with coeliac disease who were studied serially, lamina propria plasma cells and eosinophils and intraepithelial lymphocytes increased, and lamina propria lymphocytes decreased, within three months of the reintroduction of gluten to the diet. These observations are essentially similar to those made in the adult form of the disease and suggest that more than one type of immunological reaction is involved in the pathogenesis of the jejunal lesion.     

A generalization of a matrix occupancy problem

An extension of the so-called committee problem is discussed in terms of the occupancy of a certain matrix whose row totals are taken as fixed, and whose cell entries are constrained to lie between zero and defined maxima. A statistic is constructed as a function of the column totals and used to test the significance of a column effect, irrespective of row differences. Two special cases when the cell maxima are constant, first within rows and second within columns, yield a covariance matrix for the column totals whose inverse may be found explicitly, and this in turn leads to a relatively simple expression for the test statistic. Applications of this generalized problem to certain health research situations are discussed, and the adequacy of a X2 approximation to the statistic's null distribution is mentioned.